Control of primary and secondary antibody responses by cytotoxic T lymphocytes specific for a soluble antigen.

BALB/c mice immunized with keyhole limpet hemocyanin (KLH) develop Thy-1+ and CD8+, KLH-specific cytotoxic T cells (Tc). Such Tc cells can lyse TNP-specific B cells activated with TNP-KLH, but not with TNP-ovalbumin. Cytotoxicity was inhibited by anti-H-2K/D antibodies, but not by anti-Ia antibodies, suggesting a major histocompatibility complex class I-restricted killing. Selective enrichment for virgin and memory TNP-specific B cells revealed that the latter cells were relatively resistant to lysis by KLH-specific Tc cells. Depletion of CD8+ T cells from cultures of TNP-specific virgin B cells activated with TNP-KLH and KLH-primed T cells, increased the titer of anti-TNP antibodies in the culture supernatants. This increase was reduced if KLH-primed CD8+ T cells were added to the culture 1 day before its termination. Anti-TNP antibody secretion by memory B cells activated in the same manner was not affected by depletion or addition of CD8+ cells. These results suggest that Tc cells are generated following immunization with a soluble antigen which may participate in the down-regulation of primary B cell responses.