286 GLADMAN, KEYSTONE, AND SCHACTER

15. Kenl JF, Fife EH Jr: Precise standardization of reagents for com­plement fixation. Am J Trop Med Hyg 12:103-116, 1963

16. Lewis EJ , Carpente r CB, Schur PH: Serum complement component levels in human glomerulonephri t is. Ann In tern Med 75:555- 560, 197 1

17. Ruddy S, Carpenter CB, Mi.iller-Eberhard HJ , Austen KF: Com­plement component levels in heredi ta ry angioneurotic edema and isolated C'2 deficiency in man. Mechanisms of inflammation induced by immune reactions. Fifth International Immunopath­ology Symposium. Edited by PA Miescher, P Grabar. Basel, Benno Schwabe & Co., 1968, pp 231-251

18. Gigli I, Rudely S, Austen KF: The stoichiometric measurement of Lhe serum inhibi tor of the first component of complement by the inhi bition of immune hemolysis. J Immunol100:1 154-ll64, 1968

19. Fearo_n DT, A us len KF, Rudely S: Properdin factor D. II . Activation Lo D by properdin. J Exp Med 140:426-436, 1974

20. Hunsicker LG, Rudely S, Carpenter CB, Schur PH, Merrill JP, Mi.iller-Eberharcl HJ, Austen KF: Metabolism of the third com­plement component (C3) in nephTilis. Involvement of the classic and alte rnate (properdin) pathways for complement activation . N Eng! J Mecl 287:835- 840, 1972

0022-202X/83/8004-0286$02.00/0 THE JOURNAL OF I NVESTIGATIV E D ERMATOLOG Y, 80:286-290, 1983 Copyright© 1983 by The Will iams & Wilkins Co.

Vol. 80, No.4

21. Wintroub BU, Mihm MC Jr, Goelz! EJ, Soter NA, Austen KF: Morphologic and functiona l evidence for release of mast-cell prod ucts in bullous pemphigoid. N Eng! J Med 298:41 7-421, 1978

22. Dvorak AM, Mihm MC Jr, Osage JE, Kwan TH, Austen KF, Winlroub BU: Bu Ll ous pemphigoid, an ul trastructural study of Lhe inflammatory response: eosinophil, basophil and mast cell granu le changes in mul tiple biopsies from one patient. J Invest Dermatol 78:91-101, 1982

23. Wintroub BU, Dvorak AM, Mihm MC Jr, Gleich GJ: Bu llous pemphigo id: cytotoxic eosinophil degranulation and release of eosinophil major basic protein. Clin Res 29:618A, 1981

24 . Ashicla ER, J ohnson AR, Lipsky PE: Human endothelial cell­lymphocyte in teraction. Endothelial cells fun ction as accessory cells necessary for mi togen-induced human T lymphocyte acti­vation in vitro. J Clin Invest 67:1490-1499, 1981

25. Orton PW, HufTJ C, Weston WL: Immunofluorescence examination of ery thema mul tiforme skin for herpes antigens (abstr). J Invest Dermatol 78:361, 1982

2() . Fritz KA, Nonis DA, Ryan SR, Huff JC, Weston WL: Herpes specific cellular cytotoxici ty induced by erythema mul tiforme serum (abstr). J Invest Dermatol 78:343-344, 1982

Vol. 80, No.4 Printed in U.S.A.

Aberrations in T -Cell Subpopulations in Patients with Psoriasis and Psoriatic Arthritis

DAFNA D. G LADMAN, M .D ., F.R.C.P.(C.), F.A.C.P., EDWARD c. KEYSTONE, M.D., F.R.C.P.(C.), F.A.C.P., AND

RICKY K. SCHACTER, M.D., F.R.C.P.(C.)

University of Toronto, Rhewnalic Disease Unit, The Wellesley Hospital (ECK, DDG) and Wom.en '.s College Hospital (RKS, DDG), and The Psoriasis Education and R e.search Center (RKS), Vl1omen 's College Hospital, Toronto, Canada

Peripheral blood T-cell s ubpopulations and B-cell numbe r s from 25 patients with uncomplicated psoriasis and 22 patie nts with psoriatic arthritis were compared with those of 24 age- and sex-matched healthy volun­teers and 11 patients with rad:iolob>ically defined erosive osteoarthritis. The numbers of early and late rosettes w e r e found to be reduced in patients with psoriasis, with and without arthritis, while the total T-cell population (measure d by aminoethylthiouronium bromide-rosettes) was found to b e normal. There was no diffe r ence in the number of B cells between psoriatic patients and con­trols. Dose-response studies of mitogen s timulation with

Manuscrip t received Apri l 29, 1982; accepted for publication October !'i, 1982.

This work was supported by a grant from Women's College Hospi ta l l{csc:nch Fund.

H.eprinl req uests to: Dr. D. Gladman, Women's College Hospi ta l, Burton Hall # 207, 60 Grosvenor Street, Toron to M5S 1B6, On ta rio, Canada.

Abbreviations: AET: aminoelhylthiouronium bromide Con-A: concanavalin A FC. : fetal calf serum HBSS: Hanks' balanced salt solu tion lg: immunoglobulin NSAID: nonsteroidal anti-in!lammatory drugs PBM: peripheral blood mononuclear cells PBS: phosphate-buffered saline PHA: phylohemagglu tinin-P PWM: pokeweed mitogen SHBC: sheep reel blood cell (s) UVll: ullraviolel radiation

phytohemagglutinin and concanavalin A revealed gen­erally highe r proliferative responses in the psoriatic pa­t ients only at supraoptimal concentrations. The poke­w eed mitogen response, however, was reduced in pa­tients with c utaneou s psoriasis and increased in patients with psoriatic arthritis. These studies further support the concept of an immunologic imbalance in lymphocyte populations from patients with psoriasis and psoriatic arthritis.

It has been proposed t hat immunologic a bnormali t ies m ay play a role in t h e pathogenesis of psoriasis a nd psoriat ic a r t lu·itis [1. ,2]. Evidence to support this t heory has accumulated in the past d ecade [3-16]. E levated levels of immunoglobulins have been found in the sera of patien ts with pso rias is and psoriatic a rth.ri t is [3,4] a nd a nti-immunoglobulin activi ty has been dem­onstrated in bot h sera [ 4-6] a nd tissues [7-9] of psoriatic patients . These findin gs have suggested a hyperactive B-cell r esponse. Studies of cell-m ediated immune response in psoriatic pati ents have been contra dictory. T h e r esults of mitogen stim­ulation studies ha ve varied and include r eports of increased, dec reased , and norma l responses [10- 17]. ImpaiTed suppressor T -cell activity has recen tly been demonstrated in both cu ta­neo us psori asis [18,19] a nd psoria t ic a rthri t is [20]. T-cell num­bers reported in the li terature have varied from low [12,13,-17,2 1-25] to normal [26,27].

The present investigation was carri ed out in order to cla ri fy some of the contra dictory results described in patients with psorias is and psoriat ic a rthritis. We have enumerated periph­eral blood T-cell subpopulations and B-cell numbers in patien ts

April1983 ABERRATIONS IN T- CELL SUBSETS IN PSORIASIS AND PSORIATIC ARTHRITIS 287

with psoriasis and psoria t ic artlu-itis a nd compared t hem to patients with e rosive osteorutlu-itis and normal con tro ls . An imbalance in T-ce!J subsets was demonstrated in patients wi t h % uncomplicated psoriasis a nd psoria tic arthritis. Dose-response st udi es of mitogen s timulat ion in these pa ti ents furth er sup- 50 ported the concept of an immunologic imbalance in these disorders.

A B

M ATERIALS AND METHODS

Patient Selection

T went y- fi ve pa l ien ts wi th psorias is, uncomplicated by arthri tis, and 22 pat ients with pso riat ic arthri t is a ttending the Psoriasis Ed ucation

40

I

A 0

0 0 0 0 • and l'tesearch Cente r (PEI{C) and the psoriatic a rt hri t is c linic at 30

Women';; College Hospita l, T oronto, were s tudied (Table I). Although topical med ications, ul! rav iole t radia tion (UVR) , a nd nons te roida l anti ­inflammatory drugs (NSAID) were a llowed, none of I hese pa tients had

I • •

0

I 0 00

00

• CD

• 0 - I CD .. ~ taken o ra l steroid ;;, ret ino ids, methotrexate, P UVA, gold, chloroquine. ZO or penicillamine prior to the s tudy. Clinical assessmen t:;; were performed I 0 I I • 8 by a dermato logi:;t and a rheuma tologis t according to a standard pro toco l. Percent skin involvement, number of ''active ly' ' infla med join ts (tenderness, s tress pa in , effus ions), and a rticular index were

00

1 0

recorded Cor each pa t ient. 10 •• .; • y Contro l.,

Twen t.v- four age- a nd sex-ma tched healthy volu nteers (hospi ta l per­sonn el) se rved as " norma l controls" and were stud ied during Lhe same Lime pe riod. An addi t iona l group o r 11 pat ien ts with radiologica lly defin ed e rosive os leoa r! hritis se rved as disease controls . All t hese pa tien ts were la king NSAID. All patients a nd contro ls ga ve an informed consent.

Cell Separation

Periph era l b lood mononucl ear .cell s (l'BM) were isolated by hy­paqu c-F ico ll gradient centrifuga tion [28l Th e sepa rated cells were washed twice with a lpha medium (National Cancer Institute, T oronto) con! a inin g- 50 U/ ml penicill in , .~0 /lg/ml slreptom.vc in, and 2 mM/ ml L­g lutanline.

E -R o.-;ett es

E-rose t tes were pe rformed b.v resuspending PBM in phospha te­buffe red saline (PBS ), pH 7.4, in a concen t ration of 3 X tOn ce lls/ mi. One hundred microlite rs or ce ll suspension were add ed to 100 ~d of a 1% sheep reel blood cell (SHBC) suspens ion and incuba ted at 37°C for 15 min. Ea rly rose t tes were enumera ted immedia tely fo llowing centrifu­ga tion of the ce ll mix! ure at 1000 rpm for 5 min a t mom tempera! ure. Late mseUes were prepa red in a s imi la r fashion except tha t the result­ant pelle t was incuba ted ove rnigh t a t 4°C and resuspended prior Lo coun ting. For de tection of t he tota l E- roseLLing popu la tion , 1 vol or 5% SHBC was pre incuba tcd for 20 min a ! 07°C with 4 vol of 0.14 M aminoethylthiouronium bromide (AET) (S igma, (. Louis, Missouri) , and washed with PB. prior to the ir add it ion to t he PBM suspension. The l'BM-SRBC mixture was centrifuged at 2000 rpm for 1 min and

TARL to: I. Clinical data of patients with' uncomplicated psoriasis and psoriatic arthrit is

Number or patients Male/female Mean age (ra nge) Mean disease duration in years

(range): Sk in Jo in ts Mean percent skin in volvement

(range ) Mea n number o f "act ive'' joint s

(± SE) Mean Lansbury Articula r Ind ex

(± SE) T herapy (number of pat ients ) N il UVJ Topica l s tero id NSAJD

Pso ri a.s i ~

25 20/ 5

. 4 1 (21-74)

16.5 (1-4 3)

14 (2-73)

12

8

Psori at. i<.: a rLhrit is

22 9/ 13

52 (24- 76)

11 .0 (2.5-55) 7.0 (0.1-30) IG (0.5-75 )

12 ± 2

24 ± 7

10 5 7

16

• •

PSORIATIC PSORIASIS ARTHR I Tl S

Ft G I. Ea rly E-rosettes in pa tients with psoriatic art hJ·it is (A) and uncomplicated pso riasis (B). In each pa ne l, x depicts the mean response and the error bars represent ± SE. Patients are represented by (e) a nd age- and sex-matched hea lthy con trols by 0 .

t he pell et immediate ly resuspended for enumeration of t he msettes. In all the roset Le assays, the pe lle t was gently resuspend ed a nd the suspension transferred to a hemocytometer cham bet· for coun ting. T wo hundred ce lls were coun ted and i he pro pori ion of PB M binding 3 or more SHBC was detenninecl. Immunoglobulin (!g) -bearing lymph o­cytes were de tec ted b.v us ing techniqu es of aMi-immunoglobulin flu o­rescent st ain ing. Brien.v PBM. in a concentration of 4 x 10'; ce lls/ ml were resuspended in Ha nks' ba lanced sa lt solution (HBSS) and 5CJ; feta l ca lf' se rum (FCS). Fifty microli te rs of I he cell suspension was incubated with 50 11l of fl eurescein iso thiocyanate (FITC)-conjugated (Fab ' )" goat an tihuman Ig (Cappel La borator ies, T oronto, Onta rio) for 30 min at 4°C. Following centrifuga tion a t 500 rpm for 5 min a t 4°C the supernatant was removed and t he cells washed tw ice with HE SS and 5% FCS mixed with 50% glycerine. The suspens ion was t ransferred to s lides incuba ted fo r 10 min in !.he cold and read with a Leit z-Ort holux microscope with flu orescence ve rtical and phase contrast illumina tors. Two hundred ce lls were counted and the percen tage of nuorescing ce lls determined.

Mito{fen -Induced Lymphocyte Transformation

PBM were resuspended in a lpha medium conta ining IO'ii· pooled human AB serum. Triplica te 200-111 cultures each cont a ining 5 X JOH ce lls were se t up in fl a t-bol! omed Linbro microlite r we lls. Fi fty micro­li ters of mitogens was added to each cul t ure in va rying concent.rat ions as fo llows: phy to hemagglutini n-P (PI--TA) (Welcome, England ) 0.6. 2.25, 4.5, 18, 180 ~tg/cu l tu re, concanavalin A (Con-A ) (Calbiochem. La Jo lla. Ca lifornia) 0.5, 1.0 and 2.0, 40, 80 /lg/ cult ure, and pokeweed mit ogen PWM (GIBCO Grand Island , New York ) 0.1, 0.5, I , 20 dilution x 10 ;'/ cul ture. J'BM incuba ted with PHA a nd Con-A were cul tured fo r 5 days and those incubated with PWM were cultured for 7 days. Tritia t~d thymidine (0.2 ,,Ci/ culturc, sp ac! 18.4 Ci/ mmol) was added 4 h prior to harvest.. Trit ia ted thym idine incorporation was dete rmined by liquid sc intillation counting. S ta tis t ica l a na lys is of the di fferences between groups was determined by Lh c S tudent t-test a nd t.he Mann-Whitney rank sum test.

RES ULTS

Lymphocyte Su bpopu La I ions

Analysis of ea rly rosettes in 25 patients with uncomplicated psoriasis a nd in 11 patients with psoriatic a rthritis revea led

288 GLADMAN, KEYSTONE, AND SCHACTER Vol. 80, No. 4

TABLE Il. Lymphocyte nwrhers (rom patients with u.ncomplicated psoriasis, psoriatic arthritis, and osteoarthritis and healthy control:;

Lymphocy te marke r

Ea rly rosettes Late rosettes AET-roselles AET+;E-Ig-bearing cells (B)

Numbers refer to mean values± SE. NA = not assessed .

Psori atic arthritis

20.0 ± 3.0" 56.6 ± 2.01

'

82.3 ± 1.8 22.3 ± 2.9" 9.2 ± 1.5

" Difference between patient group and controls at p < 0.05. " Difference between patient group and controls at p < 0.001. ,. Diffe rence between patient group and contro ls at p < 0.005.

significantly lower percentages of early rosettes in t he psoriatic patients relative to the age- and sex-matched normal controls (F ig 1, Table II). S imila rly, late rosettes were significantly lower in both patient groups (25 patients with uncomplicated psoriasis and 22 patients wit h psoriatic arthr it is) than t hose of healthy controls a nd of patients with erosive osteoarthrit is (Fig 2, Table II) . T here were no s ignificant differences in the total rosette­form ing cell pop ulations, as measured by AET-rosettes, among the groups of patients with uncomplicated psoriasis, psoriatic a rthritis, osteoarthri t is, and healt hy controls (Ta ble II). In order to further delineate differences in E-msette formation between patients and controls, the number ofT cells forming rosettes with AET-treated SRBC but negative in the late E­rosette assay (AET4 ;E- ) was calcu lated for each group (Table II). The mean number of AET+ ;E- T cells from patients with uncomplicated psoriasis and with psoriatic arthritis were sig­nificantly higher than those of patients wit h erosive osteoar­thritis and of normal controls. The number of Ig-bearing cells was not statistically different in the 4 groups of patients (Table II).

Lymphoproliferative Studies

Mitogen dose-response studies were performed on lympho­cytes from 10 patients with uncomplicated psoriasis a nd 10

% A B c

80 0

0 0

70 0 8 0 0 - ~ j t I . ~ I

I ..

I '8 I 0

60 0 . & 0

I "l" 0

I ' 0

00 cP 0 0 . 0 . 0

50 0 . 0 -r

40

30

20

10

PSOR IATI C NORMAL PSORIASI S NORMAL OS TEO - NORMAL ARTHR ITI S ARTHR ITIS

F I G 2. Late E-rosettes in pa t ients with psoriatic a rthri tis (A) , un­complicated psoriasis (B), and erosive ostcoarthri ti · (C) .ln each panel, x depicts the mean response and the error bars represent ± 1 SE. Patients are represented by e and age- a nd sex- matched healthy contro ls by 0 .

Psoriasis OA Normals

20.5 ± 2.0" NA 25.5 ± 1.8 56.8 ± 2.1 " 64.8 ± 3.0 63.2 ± 1.1 81.0 ± 1.0 82.4 ± 3.0 82.0 ± 1.4 24.7 ± 2.3'" 16.8 ± 3.5 16.6 ± 2.4

9.1 ± 1.3 8.0 ± 1.6 10.1 + 1.4

patie nts with psoriatic arthri t is and compared to those of age­and sex-matched healthy controls. As shown in Fig 3, t here was no s ignificant difference in peak responses to PHA between patients with psoriasis and norma l contro ls. However, at high concentrations of PHA, the r esponse of lymphocytes from patients with psoriasis was significantly higher tha n t hat of normal controls ( p < 0.05). S imilar results were demonstrated with Con-A, although the difference was not statistically sig­nifi cant. The dose-response curve to PWM of patients with psoriasis was similar to normal controls but the response was sign ificantly lower (p < 0.05) in a ll but the lowest concentration.

Lymphocytes from patients wi th psoriat ic arthri t is (Fig 4) behaved similarly, showing significantly higher proliferation only at high concen tration of PHA and Con-A. However, the peak lymphocyte response to PWM of lymp hocytes fTom pa­tients with psoriatic a rthritis was significant ly higher tha n that of controls ( p < 0.05).

100

40

0 20 . ;;; Q. 0 10

PHA

/ J ___ J ____ ~.

~-, t \1

v 1

0.6 2.25 4.5 18 180

ug/culture

CON A PWM

0.5 10 20 40 80 0.1 0.5 20

1-lQ/cu lture dilutiOn X 1 Q• lfCU1!ure

FIG 3. Mitogen stimulation studies in patients with psorias is (e)

and age- a nd sex-matched healthy controls (0 ). Each dol represents the mean coun ts per min of 10 indiv iduals. The error bars represent

±ISE.

100

40

~ • 20 ;;; Q.

0

PHA

r.....-:•.=-~ I1.- ....... I 1 1\

l \ \ ' ' ' ' ' ' ' ' v

'

0.6 2.25 4 .5 18 180

IJg/culture

CONA PWM

0.5 10 20 40 80 0 .1 0 .5 1 20

ug/cuJture di lution x 1Q•lfcu lture

FIG 4. Mitogen stimulation studies in psoriatic a rthritis (e) com­pared to age- and sex-matched hea lthy cont rols (0 ). Each dot repre­sents the mean response of 10 individuals. The error ba.rs represent ± I SE.

April1983 ABE RRATIONS IN T -CELL S UBSETS IN PSORIAS IS AND PSORIATI C ARTHRITIS 289

There was no correlation between the extent of skin disease, measuTed by percent skin involvement, a nd percent r osettes or lymphocyte reactivity to mitogens of patients wit h psoriasis. H owever, patien ts with psoriatic arthri t is wi t h early rosettes of less than 25% had significant ly higher join t coun ts tha n t hose with normal (> 25%) early rosette coun ts (p < 0.001) . There was no r ela tionship between roset te numbers a nd the use of either U VR therapy or topical steroid therapy .

DISCUSSION

Immunologic abnormalities a re considered importa nt factors in the pathogenesis of psoriasis [1 ,2]. A cen tral r ole for T -cell dysfunction h as been sugge ted [1,2,10-24]. Reduced numbers of E-rosette-forming cells in psoriasis have been r epor ted by several investigators [12,13,20-24]. T he present study has dem ­onstrated reduced levels of early and late E-rosettes in patients with cutaneous psoriasis and with psoriatic ar thri t is, as com­paTed to normal contr ols and to patients with erosive osteoar­tru·it is. H owever, AET-rosettes, which measure t he total T -cell population, were normal. These r esul ts did not correlate wi th the use of UVR or topical steroid thera py. P a ti ents wi th os­teoar thri t is were also taking N SAID and the i1· r esul ts were norma l. We t herefore feel that our resul ts do not represen t d1·ug effect.

Eru·Iy rosettes are cons idered to be a subpopulation of T cells wi th high a ffini ty for SRBC [29- 31]. These cells m·e though t to serve as effecto r cells a nd may r efl ect more closely the in vivo immune response pattern [30,31]. D epressed levels of early rosettes have been shown in some patients wi th cer tai n malig­nant condi t ions a nd immunode.ficiency states [29,30]. Al though the diminu tion of early rosettes in patients wi t h psoriasis a nd psoria tic ar thr it is did not correlate wi th the extent of skin disease, low roset te numbers correlated with more severe joint disease.

Our findin gs of low late rosette-forming cells confim1 previous reports of low T cells. Guilhou a nd coworkers [12,13], C01·mane et al [21], Glinski et a l [22], and Sany a nd Clot [17] have all observed decreases in late rosette-forming cells in patients with psoriasis and psoriatic ar thri t is. We, like Glinski et al [22], fo und no corre lation between the extent of skin disease and T­cell levels.

It has been suggested that the decrease in T cells noted in patients with pso riasis may refl ect a reduction in or the a bsence of clones of suppressor cells [1]. We and others have shown that the re is a suppressor cell defect in both psoriasis and psoriatic arthri t is [18-20]. M ore recently, we have confirmed an imbal­ance in the immunoregula tory T-cell populations in patients with psoriatic a rthri t is [32]. Using orthoclone monoclonal ant i­bodies, we have shown that patients wi th psoria tic rutru·it is had decreased levels of OKT 3 (T cells), a nd OKT 8 (suppressor­cytotox ic cells ). An increase in t he OKT 4 to OK T 8 ratio was demonstrated , suppor ting our content ion that there is an im­balance in T-cell subpopulations.

In the present study, t he total T-cell population as measured by AE T-rosettes was found to be normal in th e face of reduced early a nd late E-rosettes. Such ·differences between AET-ro­settes and late E -rosettes have been previously described in a variety of unrelated condi t ions [33]. This discrepa ncy may be re lated to an actual al teration in lymphocyte subpopulations, or it may suggest the presence of an immature population of T cells. It has been shown t hat the incubation of mononuclear cells from patients wi th rheumatic diseases wi th thymosin led to an increase in E-rosette-forming cell numbers [34,35]. It has been suggested that thy mosin effect proba bly represents stim­ulation ofT-cell maturation from precursor cells [33- 35]. It is possible that t he differ ences observed in the present study refl ect a n increased number of immature T cells in the periph­eral blood of patients wi th psoriasis a nd psoriatic artlui t is. Other possibilities, however, could accoun t for t he differences between AET- and E-roset te-formin g cell numbers . There may be a reduction in the affini ty and/or numbers of SRBC recep-

tors as a consequence of interfering humor al substances. Indeed, a ntily mphocyte a nt ibodies have been shown to redu ce the number of E-rosette-forming cells detected in cer tain disease states [36,37]. Gelfand et al [33] have shown that T -cell antisera can inhibi t E -rosette formation, but that a much higher con­centration of antiserum was req uired to inhibi t AET-rosettes. Al though such ant ilymphocyte a nt ibodies have not been re­ported in psoriasis and psoriatic arthri tis, the presence of a nti­stra tum corneum antibodies a nd an a nt ibody to basal cell nuclei have been demonstrated in t he sera and lymphoid cell mem­branes in patien ts wi th psoriasis [2]. Immune complexes have a lso been demonstrated in t he sera of patients with both pso­riasis a nd psoriatic arthTitis [27), a nd t hese too could interfere with SRBC receptors. W hether the red uced numbers of cells with receptors for late and eru·ly E-rosette-forming cells repre­sent an aberration in recep tor interaction or a deletion in lymphocyte subpopulations remains to be determined. Studies are current ly under way in our laboratory to discern the func­t ional characteristics of t he AET+ IE- cell population in relation to immune regulatory activity .

Reported data concerning ly mphoproliferative responses to mi togens in uncomplicated psoriasis a nd in psoriatic ar thritis have been conflicting. Whereas Levant ine a nd B rostoff [11) reported a decreased response to PHA in patients with psoriasis, both Guilhou et al [12) a nd Clot a nd Guilhou [13] reported normal responses. In psoriatic artlui t is, Sany and Clot [17] demonstrated a normal lym phocyte response to PHA, while Espinoza et al (15] reported a decreased response in such patients. Frobel eta) [10] observed that, at h igh concentrations of PHA, lymphocytes fro m 11 patients with psoriatic arthr it is were hyperreactive compared to normal con trols. T he present study may provide an expla nation for the discrepa ncies of the previous repor ts. We found that, at high concen trations of mi togen, ly mphocytes from patien ts wi th eit her uncom plicated pso riasis or pso riatic ar t hri t is were hyperreactive, whereas at the lower (more op timal) concentrations, th e r esponses were either normal or slightly reduced . T he response of lymphocytes fTom pa tients with psoriasis to Con-A has been obser ved to be low by several investigators [12,13,15] and normal by others [16,19]. We fo und that, with high concen trations of Con-A, as with PHA, lymphocytes fr om psoriatic patients were h yper­reactive. P WM responsiveness was reported to be low in pa­t ients wi th cutaneous psoriasis by Guilhou and coworkers [12,13). We found similar resul ts in our patients with psoriasis. The dose-response curve of lymphocytes of patients with pso­riatic a rthri t is to PWM was parallel to the normal cm ve, bu t t heir responses were higher at each concentration . T his latter resul t is in disagreement with previous repor ts of low [15] or norm al [17] r esponses to P WM in these patients. The abnor­mali t ies in lymphocyte responsiveness to mitogens observed in patients wi t h psoriasis and psoriatic arthr it is and the close­response kinetics may resul t from the abnormali ties in T-cell su bpopulations described, and may indeed reflect the presence of immature cells which require higher dose of mitogen for response.

In summary, we have demonstrated abnormali ties in T-cell subpopula tions in patients wi th uncompli cated psoriasis a nd psoriatic ar thri t is. T hese abnormalt ies may lead to abnormali­t ies in T -ceU function. This supports the concept t hat immu­nologic a bnormali ties may be relevant in th e pathogenesis of both psoriasis a nd psoriatic a r thrit is.

The aut hors wish to acknowledge t.he helpfu l comments of Dr. Abraham Shore, the technical assistance of Mrs. Lorraine Poplonski, and Lhe secretarial assistance of Miss Nancy heridan.

REFERENCES

I . Guilhou JJ , Meynad ier J , Clot J: New concept s in the pat hogenesis of psoriasis. Br J Dermatol 98:585-592, 1978

2. C01·manc RH: Immunopathology of psoriasis. Arch Dermalol Res 270:201-2 15, 1981

:J. l<inindianin V, Mila vic J: Serum imm unoglob ulins and complement levels in patients with p. oriasis vulgaris. Allerg lm munol (Leipz) 22:143- 146, 1976

290 GLADMAN, KE YSTON E, AND SCHACTER

4. Guilhou JJ , Clot J, Meynadier J , Lapinski H : Immunological as­pects of p orias is. I . Immunoglobulins a nd ant i-IgG factors. Br J Dermatol 94:501-507, 1976

5. Rimbaud P, Meynadier J , Guilhou J J, Clot J: Anti-lgG activity on peripheral blood lymphocytes in psoriasis. Arch D ermatol 108:371-373, 1973

6. Howell FA, Chamberla in MA, Perry RA, T orrigia ni G, Roitt JM: IgG ant i-immunoglobulin levels in patients with psoriatic art hri ­t is, ankylosing spondyli t is a nd gout. Ann Rheum Dis 31:129-131, 1972

7. Krogh HK, T onder 0: Immunoglobulins and anti-immunoglobulin facto rs in pso riatic lesions. Clin Exp Immunol 10:623- 634, 1972

8. Fryand 0, Mellbye OJ , Natvig JB: Immunoflu orescence studies fo r immunoglobulins and complement C3 in synovia l joint mem­branes in psoriatic ar thri t is. Clin Exp Immunol 29:422- 427, 1977

9. Ullman S, Halberg P, Hentzler B: Deposits of immunoglobulins a nd complement in psoriatic les ions. J Cutan Pathol 7:271-275, 1980

10. F rM bel K, Sturrock RD, Dick WC, MacSween NM: Cell-mediated immuni ty in the rheumatoid diseases I. S kin testing and mi to­genic responses in sero-negative ar thri t ides. Clin Exp Immunol 22:446-452, 1975

li . Levan t ine A, Brostoff J : Immunological response of patients with psoriasis and the effec t of treatment by methotrexate. Br J Dermatol 93:659-666, 1975

12. Guilhou J J, Meynadier J , Clot J , Charmasson E , D ardenne M , Brochier J : Immunological aspects of psoriasis. II. Dissociated impairment of thymus-dependent ly mphocytes. Br J Dermatol 95:295-301, 1976

13. Clot J, Guilhou JJ : P erturbations immunologique au cours du psorias is cutane. Revue du R heumatisme 46:539- 546, 1979

14. Krueger GG, Hill HR, J edenberg WW: Infla mmatory a nd immune cell function in psoriasis-a subtle disorder. 1. In vivo and in vitro survey. J Invest Dermatol 71:189-1 94, 1978

15. Espinoza LR, Gaylord SW, Vasey , Osterland CK: Cell -mediated immuni ty in psoriatic ar thrit is. J Rheumatol 7:218-224, 1980

16. Hopsu-Havu VK , Hela nder I: Cell med iated a utohypersensit ivity in psoriasis. Acta DertnVenereol (Stockh) 54:333- 337, 1974

17. Sany J, Clot J : Immunological a bnormalities in psoriatic ar t hTo­pathy. J Rheumatol 7:438-444, 1980

18. Sauder D N , Bailin PL, Sundeen J , Kra kauer RS: Suppressor cell function in psoriasis. Arch Dermatol 116:51-55, 1980

19. Hunyadi J , Dobozy A, Kenderessy AS, S imon N : S uppressor func­t ion of periphera l blood mononuclear cells in patients with pso­riasis vu lgaris. J Invest De rmatol 75:217-218, 1980

20. Gladman DD, Keystone EC, Russe ll ML, Schachter RK: Impaired antigen speci!lc suppressor ce ll activity in pso riasis and psoriatic arthri tis. J Invest Dermatol 77:406-409, 1981

21. C01·mane RH , Hunyadi J, Ha merlinck F : Mechanismes immuno-

Vol. 80, N o. 4

logiques du psoriasis. Ann Dermatol Syphiligr 103:567- 572, 1976 22. Glins ki W, Haftek M, Oba la k S, J ab lonska S: Clinical aspects of T

and B ly mphocytes in psoriasis. Arch D ermatol R es 258:89-92, 1977

23. Clot J , Guilhou J J, Meynadier J , Parad is B, Andary M: Immuno­logical aspects of psorias is. Ill. Fc-receptor bearing mononuclear ce lls in peripheral blood. B r J Dermatol 99:25-30, 1978

24. Glinski W, Obalek S, Langer A, J ablonska S , H aftek M: D efective fun ction ofT ly mphocytes in psorias is. J Invest D ermatol 70: 105-110, 1978

25. Lischka G: T -lymphocytes and psoriasis. Arch Dermatol Res 257: 107- 108, 1976

26. Wassilew SW: Stimulation oflymphocytes in patients wi th psoriasis under photochemothera py. Arch Dermatol R es 263: 127-1 30, 1978

27. Karsh J , Espinoza LR, Dorva l G, Vasey F, Wilkinson R, Osterla nd CK: Immune complexes in psoriasis with a nd without artl11"i tis. J R heumatol 5:314- 319, 1978

28. Perper PJ , Lee TW, Michelson MM: P uri!lca tion of lymphocytes a nd plate lets by gradient centr ifugation. J Lab Clin M ed 72:842-848, 1968

29. Wyb ran J , Fudenberg HH: Thymus-derived rosette-forming cells in various huma n disease states: cancer, ly mphoma, bacterial a nd vira l infections, a nd other diseases. J Clin Invest 52:1026-1032, 1973

30. Horowi tz S, Groshong T, Albrecht R, H ong R: The 'active' rosette test in immunodeficiency diseases. Clin Immunol Immunopathol 4:405- 414 , 1975

31. Yu DTY: The response of huma n early and late rosette- forming lymphocytes to mixed and a uto logous ly mphocyte cul ture a nd mi togens. Clin lmmunol Immunopathol 10:11-18, 1978

32. Keystone E C, Lau L, Gladma n DD, Wilkinson S, Lee P , Shore A: Immunoregulatory T -cell subpopulations in pa tients wi th scle­roderma using monoclona l antibodies. Clin Exp Immunol 48:443-448, 1982

33. Gelfand E W, S hore A, Green B, Lin MT, D osch l-I-M: The E­rosette assay: a caut iona ry note. Clin Immunol lmmunopathol 12:119-123, 1979

34. Moutsopoulos H , Fye KH, Sawada S, Becker MJ , Goldstein A, T ala! N: In vit ro effect of thymosin on T -l:vmphocyte rosette fo rmation in rheumatic diseases. Cli n Exp Immunol 26:563-573, 1976

35. Michalevicz R , Many A, Ra mot B, Tra in inN: The in vitro effect of thymic humoral factor and levamisol on peripheral blood lym­phocytes in systemic lupus erythematosus patients. Clin Exp lmmunol 31:11.1-115, 1978

36. Del Giacco GS: Anti-lymphocyte ant ibodies and diseases, Devel­opments in Clinical Immunology. E di ted by M Ricci, AS Fauci, P Arcangeli, P T orzuoli . London, Academic, 1978, pp 129-138

Three Bill R eed International Travelling Fellowships will be awarded this year as follows: The winner of the Poster Session a t the annual meeting of the European Society for D erma tological R esearch will

be awarded $800.00 to help support a trip to a ttend the annual meeting of the American Academy of Dermatology. The winner of the Stelwagon Prize for the best paper presented at the Residents' Forum a t the annual American

Academy of D ermatology meeting will receive an $800.00 award to support a trip to Europe where the awardee will present a paper at the annual meeting of the British Associa tion of Dermatologists in England. Further travel to European centers can also be arranged.

An award of $800.00 will be given to an academically oriented dermatologist in the private practice of clinical dermatology, who has been out of training no more than five yea1·s. It is meant to support travel for educational purposes and to broaden contacts with dermatologic investigators. Applicants should send ·their cw-riculum vitae and a covering letter, indicating how he/she plans to spend the award funds, to the Chairman of the Committee on International Affairs of the A.A.D . at the Academy office, 1567 Ma ple Avenue, Evanston, Illinois 60201. The deadline for submission is September 1, 1983. Supporting let ter from a broad relevant to the planned travel are desira ble. The award will be announced in December and will be based on the originality and productivity of t he applicant as well as the meritoriousness of the travel pla ns for continued clinical investigation.