Differential effect of staphylococcal enterotoxin B upon the induction of tolerance on peripheral CD4+V beta 8+ and CD8+V beta 8+ T cells

Abstract

It is known that bacterial superantigens can interact with certain V beta elements of the T cell receptor to result in the activation, expansion, anergy, and/or deletion of T cells. The induction of peripheral T cell tolerance in AKR/J mice was examined in relation to the amount of staphylococcal enterotoxin B (SEB) administered and it was found that the events leading to the induction of tolerance of V beta 8+ T cells was dependent on the initial dose of superantigen employed. Following administration of a large amount (> or = 10 micrograms) of SEB into AKR/J mice, expansion of both CD4+V beta 8+ and CD8+V beta 8+ T cells was observed. This initial cell expansion was followed by the decline in the number of CD4+V beta 8+ T cells. The number of CD8+V beta 8+ T cells, however, did not decline and remained high. When a small amount (2 micrograms) of SEB was employed, it did not stimulate T cell expansion in AKR/J mice. However, when these mice were challenged with SEB, anergy was observed in the CD4+V beta 8+ T cells regardless of the initial dose of SEB. In contrast, the CD8+V beta 8+ T cells were not anergized and were able to proliferate on stimulation with a second dose of SEB. The state of anergy for the CD4+V beta 8+ T cells lasted for at least 70 days, and by 150 days the anergic state was relieved and these CD4+V beta 8+ T cells were once again able to proliferate in response to SEB. On the other hand, continuous SEB exposure resulted in the decline of both CD4+V beta 8+ and CD8+V beta 8+ T cells. Although the number of CD4+V beta 8+ and CD8+V beta 8+ T cells apparently returned to normal levels by 150 days, the state of anergy persisted, as demonstrated by the reduction of the response of these T cells following SEB stimulation in vitro. Our data suggest that the initial expansion of T cells is not an absolute prerequisite for the induction of peripheral T cell anergy. Moreover, the continuous presence of superantigen is essential for the deletion and maintenance of a state of anergy for CD8+V beta 8+ T cells.