DIFFERENTIAL EFFECT OF STAPHYLOCOCCAL-ENTEROTOXIN-B UPON THE INDUCTION OF TOLERANCE ON PERIPHERAL CD4(-BETA-8(+) AND CD8(+)V-BETA-8(+) T-CELLS()V)

It is known that bacterial superantigens can interact with certain V b eta elements of the T cell receptor to result in the activation, expan sion, 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 th at the events leading to the induction of tolerance of V beta 8(+) T c ells was dependent on the initial dose of superantigen employed. Follo wing administration of a large amount (greater than or equal to 10 mu g) 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 f ollowed 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 rem ained high. When a small amount (2 mu g) of SEB was employed, it did n ot 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 o n stimulation with a second dose of SEB. The state of anergy for the C D4(+)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 wer e 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 be ta 8(+) and CD8(+)V beta 8(+) T cells apparently returned to normal le vels by 150 days, the state of anergy persisted, as demonstrated by th e reduction of the response of these T cells following SEB stimulation in vitro. Our data suggest that the initial expansion of T cells is n ot an absolute prerequisite for the induction of peripheral T cell ane rgy. Moreover, the continuous presence of superantigen is essential fo r the deletion and maintenance of a state of anergy for CD8(+)V beta 8 (+) T cells. (C) 1994 Academic Press, Inc.