CYTOTOXICITY AND WEAK CD40 LIGAND EXPRESSION OF CD8(-2 CYTOTOXIC T-CELLS RESTRICTS THEIR POTENTIAL B-CELL HELPER ACTIVITY() TYPE)

Naive CD8(+) T cells differentiate into distinct cytokine-secreting su bsets: T helper (Th)1-like cytotoxic T cells (Tc1) and Th2-like Tc2. A lthough Th2 cells provide strong B cell help, we show that Tc2 cells s ecreting the same cytokines provide only modest B cell help for IgM pr oduction, and only when large numbers of B cells were stimulated with small numbers of Tc2 cells. Lack of effective B cell help by Tc2 cells was attributable partly to their cytotoxicity towards B cells. Both T c1 and Tc2 cells killed small resting B cells mainly by a perforin-dep endent mechanism. In contrast to normal Tc2 cells, perforin-deficient Tc2 cells failed to kill small resting B cells and induced IgM and IgG 1 production, although their B cell help was significantly lower than that mediated by Th2 cells. This may be partly attributable to the abi lity of Tc2 but not Th2 cells to kill activated B cells even in the ab sence of perforin. Plate-bound anti-CD3 antibodies inhibited Tc2 killi ng of B cells and induced substantial immunoglobulin production. Addit ionally, Tc1 and Tc2 cells failed to express CD40 ligand (CD40L), wher eas Th1 and Th2 cells expressed high levels of CD40L. Stimulation of T c1 and Tc2 cells with plate-bound anti-CD3 antibodies for extended per iods resulted in low-level expression of CD40L. Proliferation of small resting B cells correlated with immunoglobulin production: proliferat ion was promoted strongly by Th1 and Th2, weakly by normal Tc1 and Tc2 , and moderately by perforin-deficient Tc1 and Tc2 cells. Thus, Tc2 ce lls may not contribute significantly to cognate B cell help during nor mal responses.