IMPLANTATION OF IL-2-CONTAINING OSMOTIC PUMP PROLONGS THE SURVIVAL OFSUPERANTIGEN-REACTIVE T-CELLS EXPANDED IN MICE INJECTED WITH BACTERIAL SUPERANTIGEN

In the present study we investigated the mechanism of deletion of supe rantigen (sAg)-reactive T cells expanded in sAg-injected mice, In stap hylococcal enterotoxin A (SEA)-injected mice, IL-2 activity in serum p eaked at 1 to 3 h and the expression of IL-2R alpha-chain (IL-2R alpha ) on SEA-reactive (V beta 3(+), or V beta 11(+)) T cells peaked at 6 t o 12 h after the injection. Expansion of V beta 3(+) or V beta 11(+) T cells peaked at 2 days after the injection when most of these T cells were IL-2R alpha negative, and IL-2 activity was not detected at all in serum, suggesting the involvement of IL-2 deprivation in the deleti on of expanded T cells, Implantation of an osmotic pump containing hum an rIL-2 (IL-2 pump) prolonged the expanded states of V beta 3(+) or V beta 11(+) T cells in SEA-injected C57BL/6 mice and of V beta 8(+) T cells in SEB-injected MRL +/+ and Fas Ag-defective MRL-lpr/lpr mice, A dult thymectomy did not change at all the effect induced by implantati on of IL-2 pump, DNA fragmentation was blocked substantially in mice c o-treated with SEA and IL-2 pump. In addition, CD4(+) T cell blasts, o btained by in vitro stimulation with rIL-2 of splenic CD4(+) T cells f rom mice co-treated with SEA and IL-2 pump, produced substantial amoun ts of IL-2 upon restimulation with SEA, These results indicate that de privation of IL-2 is deeply involved in the deletion of expanded sAg-r eactive T cells and their anergy induction in sAg-injected mice.