Helper effector function of human T cells stimulated by anti‐CD3 mAb can be enhanced by co‐stimulatory signals and is partially dependent on CD40‐CD40 ligand interaction

摘要

AbstractIn this study we have investigated whether anti‐CD3‐induced human T cell help for immunoglobulin production could be enhanced by co‐stimulation of the T cells via other T cell surface molecules, and the contribution of CD40‐CD40 ligand interaction to the execution of T helper effector function induced by these different stimulatory signals. In a system in which irradiated tonsillar T cells were stimulated with immobilized anti‐CD3 monoclonal antibody (mAb), it was found that ligation of CD2 with a mitogenic pair of mAb considerably enhanced anti‐CD3‐induced T cell help for immunoglobulin production. Likewise, ligation of CD28 with mAb enhanced T helper activity, although to a lesser extent. Upon addition of anti‐CD28 and anti‐CD2 mAb together, an even higher immunoglobulin production was observed. This combination resulted in a four‐ to fivefold increase in immunoglobulin production as compared to cultures in which T cells were stimulated with anti‐CD3 mAb alone. The effect of ligation with B7, the natural ligand of CD28, was studied in a system which utilizes the presentation of anti‐CD3 mAb on human FcγRII‐expressing mouse fibroblasts which were co‐transfected with human B7. It appeared that B7 could stimulate help for immunoglobulin production much more efficiently than ligation of CD28 with mAb did. Physical separation of B cells from T cells led to complete abrogation of immunoglobulin production. Blocking of CD40 with specific mAb, which have no intrinsic B cell stimulatory properties, or the CD40 ligand with a soluble CD40‐human IgM fusion protein, resulted in dose‐dependent, but only partial, inhibition of T cell‐dependent immunoglobulin production with all modes of T cell activation tested. A clear correlation was found between the induction of CD40 ligand expression on the T cells by the different modes of co‐stimulation and subsequent immunoglobulin production by the B cells. It is concluded that ligation of CD28 and/or CTLA‐4, and of CD2 can generate co‐stimulatory signals for T cell help for immunoglobulin production, which was found to be only partially depen