analyses, we have been able to identify highly immunogenicClass I and Class II peptides from CMV. Using syntheticantigen presenting cells, we plan to select and expandpeptide-specific CD8+ and CD4+ T effector cells suitable forimmunotherapy.

doi:10.1016/j.clim.2006.04.476

Su.50. Distinct Regulatory T-Cells Induced ByRepeated Injection of Toxic Shock SyndromeToxin-1: A Comparative Study with StaphylococcalEnterotoxin a.Haowei Li, Anthony Chow. Department of Medicine,University of British Columbia, Vancouver, BC, Canada.

Bacterial superantigens could activate a large number ofCD4+ T-cells by cross-linking MHC Class II molecules andspecific Vh segments of the T-cell receptor (TCR), triggeringmassive proliferation and cytokine production. Previousstudies showed that repeated injection of superantigens,such as staphylococcal enterotoxin A (SEA) could induce CD4+regulatory T-cells (Tregs), but not much is known about Tregsinduced by toxic shock syndrome toxin-1 (TSST-1). Weperformed a side-by-side comparative study of Tregs inducedby TSST-1 and SEA in C57B6 mice. Our data showed that TSST-1-induced Tregs had higher expression of CD25 and CTLA-4and produced higher levels of IL-10, IFN-g and TNF-a thanSEA-induced Tregs. Interestingly, both TSST-1 and SEA-induced Tregs were proliferative in response to superantigenstimulation, however, TSST-1-induced Tregs proliferatedmore potently and even in the absence of superantigenstimulation. Moreover, in vitro co-culture experimentsshowed that TSST-1-induced Tregs could downregulate thecytokine responses triggered by either TSST-1 or SEA, whileSEA-induced Tregs could only downregulate the cytokineresponse induced by SEA but not TSST-1. In vivo experimentsfurther demonstrated that induction of Tregs with TSST-1protected mice against lethal shock challenge by either TSST-1 or SEA, while induction of Tregs with SEA could only protectmice against SEA. Analysis of the Vh segments of the TCRsshowed that the broader suppressive function of TSST-1-induced Tregs was not due to the presence of overlapping Vh-reactive TCRs in these mice. In summary, our results showedthat TSST-1-induced Tregs were more proliferative and hadmore potent and broader suppressive activities, which mightbe advantageous for their potential therapeutic applicationsin immunotherapy for various clinical conditions.

doi:10.1016/j.clim.2006.04.477

Su.51. Scv-07 Peroral Formulation Protects MiceAgainst Experimental Tuberculosis Infection.Alexander Petrov,1 Natalia Pigareva,1 Alexander Kotov,1

Tatyana Vinogradova,2 Natalya Zabolotnyh,2 CynthiaTuthill,3 Alexander Kolobov,1 Andrey Simbirtsev.11Immunology, Verta, St. Petersburg, Russian Federation;2Experimental Immunology, Institute ofPhtysiopulmonology, St. Petersburg, Russian Federation;3 Pharmacology, SciClone Pharmaceuticals, Inc.,San Mateo, CA

SCV-07 is a novel peptide immunomodulatory drug. Thegoal of the present study was to compare the immunologicalactivity of a peroral formulation and i.p. injections of SCV-07 in intact healthy mice and in an experimental tubercu-losis model. In accordance with our previous results wefound elevated IL-2 activity in supernatants from ConA-stimulated spleen cells in animals treated with 0.1 and 1.0ug/kg SCV-07 i.p. Peroral administration of 0.1, 1.0 and 10.0ug/kg of SCV-07 also led to elevated IL-2 production. We alsodetected substantial changes in thymocytes subpopulations,which were most intensive in groups treated with 1.0 ug/kgSCV-07 i.p. or per os. We found an approximately 10—25%decrease in the percentage of double-positive thymocytesaccompanied with a 5—10% increase of double-negative anda 10—15% increase of CD4+ single-positive cells. To assessthe protective activity of peroral formulation of SCV-07 in anexperimental tuberculosis model, 4—6 week old C57BL/6mice were inoculated i.v. with M.tuberculosis Erdman.Starting from day 12th after challenge, all mice weretreated with isoniazid and rifampicin and divided intoseveral groups that were additionally treated during 5 dayswith 0.1—1.0 ug/kg SCV-07 i.p. or 0.1—10.0 ug/kg SCV-07per os. At day 45th after challenge there were significantlyreduced macroscopic signs of pathology and significantlylower bacterial burden in lung tissue of animals treated with1.0 ug/kg SCV-07 i.p. or per os compared to the controlgroup. These findings were accompanied by a dramaticincrease in BCG-specific proliferation and a decrease inBCG-induced IL-10 production by spleen cells in SCV-07treated groups. Based on these findings, we suggest that theperoral formulation of SCV-07 retains its immunomodulatoryproperties and is as effective in protection against exper-imental tuberculosis in mice as parenterally administereddrug.

doi:10.1016/j.clim.2006.04.478

Su.52. CD4+CD25brightFOXP3+ Regulatory T-CellsAre Induced After Cardiac Surgery.Alvin Schadenberg,1 Bas Vastert,1 Jola Evens,3 Wietse Kuis,1

Hans van Vught,2 Koos Jansen,2 Berent Prakken.1 1PediatricImmunology, Wilhelmina Children’s Hospital, UMCU,Utrecht, Netherlands; 2Pediatric Intensive Care, WilhelminaChildren’s Hospital, UMCU, Utrecht, Netherlands;3Pediatric Cardiothoracic Surgery, Wilhelmina Children’sHospital, UMCU, Utrecht, Netherlands.

Cardiac surgery induces a systemic inflammatory re-sponse. The balance between pro- and anti-inflammationis critical in determining clinical outcome. Little is knownwhether CD4CD25brightFOXP3+ regulatory T-cells play anactive role in controlling acute inflammation followingcardiac surgery. We investigated the kinetics of regulatoryT-cells after cardiac surgery in children. Twenty childrenwere investigated. Peripheral blood mononuclear cells wereisolated before, immediately after, 24 and 48 hours aftersurgery and analysed by flowcytometry. In sorted CD4CD25populations FOXP3 mRNA, was determined in 8 patientsby semi-quantitative real-time PCR. Flowcytometric analy-sis shows a significant increase (+57%, p b 0.05) in

Abstracts S177