T cell deletion and unresponsiveness induced by intrathymic injection of staphylococcal enterotoxin B

Intrathymic injection of alloantigens appears to be the most efficient rout e to induce alterations of T cell reactivity. In the present study, we expl ored the modifications of V beta 8.1, 8.2 T cell population and T cell reac tivity in the thymus and in the spleen induced by intrathymic injection of staphylococcal enterotoxin B to adult mice. V beta 8 antigen expression was investigated by flow cytometry analysis. T Cell reactivity was studied in vitro by the proliferative response to SEE. SEE induced a significant reduc tion in the percentage of mature V beta 8(+) T cells in the thymus (days 7- 14), and in the spleen (days 7-28). Interestingly, this depletion occurs in the CD4(-)CD8(+) cells in the thymus whereas in the CD4(+)CD8(-) cells in the spleen. In parallel, the proliferative response to SEE but not to SEA w as significantly decreased in the thymus on days 7 and 14, and in the splee n from day 7 to day 28. Moreover, this unresponsiveness was more pronounced in the spleen than in the thymus. Anergy was SEE-specific and fully revers ed by exogenous IL-2. SEE injected intrathymically induced significantly mo re pronounced and more durable T cell alterations than intraperitoneal and subcutaneous injections. This may be related to the observation that after i.t. injection, SEE was detected both at a higher amount and for a longer p eriod in the central and peripheral compartments. Our results clearly demon strate that the intrathymic route is definitely the most efficient to induc e not only thymic but also peripheral pivotal immune alterations in our mod el. (C) 2000 Elsevier Science B.V. All rights reserved.