THE EFFECT OF ANTI-CD4 ON HELPER FUNCTION OF CD4,45RA(+) VERSUS CD4,45RO(+) T-CELLS

Here we have investigated and compared the effects of anti-CD4 on helper function of CD4,45RA(+) versus CD4,45RO(+) T cells. Only CD4,45RO(+) cells, but not CD4,45RA(+) cells were able to promote B cell differentiation resulting in immunoglobulin production in vitro (IgM as well as IgG) which could be inhibited by anti-CD4 MoAbs (MAX.16H5 and T151). In pokeweed mitogen (PWM)-induced B cell proliferation a similar pattern of responsiveness was obtained. When we studied the anti-CD4 effects on cytokine production in T cells stimulated in mixed lymphocyte reaction (MLR) or by mitogens, we found that neither IL-2 nor IL-4 production was dramatically influenced by anti-CD4 in CD4,45RO(+) cells. This led us to the conclusion that the inhibitory effect of anti-CD4 on B cell proliferation and immunoglobulin secretion was not due to inhibition of cytokine production. To clarify this point, we investigated the ability of anti-CD4 to inhibit conjugate formation between B and T cells. It was found that CD4,45RO(+) T cells formed more conjugates than CD4,45RA(+) cells, and that only the conjugate formation by CD4,45RO(+) T cells was inhibited by anti-CD4. These results suggest that (i) anti-CD4 inhibits T helper functions primarily by affecting CD4,45RO(+) cells, and (ii) this effect is probably mediated by contact inhibition in the early phase of T-B collaboration.