DIFFERENTIAL-EFFECTS OF SUPERANTIGEN-INDUCED ANERGY ON PRIMING AND EFFECTOR STAGES OF A T-CELL-DEPENDENT ANTIBODY-RESPONSE

The in vitro T cell nonresponsiveness or anergy to restimulation with staphylococcal enterotoxin B (SEB) following the in vivo injection of the superantigen is well characterized. Here we use mice transgenic fo r a V(beta)8.2(+) T cell receptor (TcR) (reactive with SEB) to establi sh a large population of anergic T cells in vivo. As expected, periphe ral T cells from the SEB injected transgenic mice failed to proliferat e or produce interleukin (IL)-2 following restimulation with the super antigen in vitro. However, in this system superantigen reactivity coul d be restored by either addition of exogenous IL-2, or stimulation wit h immobilized anti-TcR antibody. To evaluate the effects of superantig en-induced anergy in vivo, SEB-injected or noninjected control transge nic mice were immunized and boosted with the T cell-dependent antigen tetanus toxin (TT). SEB injection of the V(beta)8.2(+) transgenic mice 5 days prior to the TT immunization inhibited the anti-TT antibody re sponse as measured over a 100-day period, whereas injection of a super antigen which does not interact with the V(beta)8.2(+) TcR (such as SE A) did not. Furthermore, SEB injection of control nontransgenic mice d id not interfere with the induction of a high titer anti-TT antibody r esponse. In contrast to the inhibition seen when SEB was given prior t o TT immunization, injection of transgenics with SEB either after the priming TT immunization or after the recall booster injection did not significantly influence the titers of anti-TT antibodies produced. The se results demonstrate that the establishment of peripheral T cell ane rgy to superantigens inhibits the specific antigenic priming of helper T cells in vivo, but does not prevent primed T cells from helping B c ells to mount an effective antibody response.