CD28 delivers costimulatory signals for superantigen-induced activation of antigen-presenting cell-depleted human T lymphocytes.

The CD28 pathway functions to provide costimulatory signals that are required for TCR-mediated activation of T cells. The role of this pathway in superantigenic stimulation of resting human T cells was investigated in the presence and absence of APC using a streptococcal superantigen, pep M5. Anti-B7/BB1 mAb inhibited the response of T cells when pep M5 was presented by APC. In the absence of APC, cross-linking CD28 by anti-CD28 mAb provides signals that synergize with APC-derived cytokines and with superantigen resulting in T cell proliferation. Anti-HLA-DR, -DQ mAb blocked the response of T cells to pep M5 presented by APC but had no effect on the response of purified T cells to the superantigen costimulated via CD28 cross-linking. These data show that the CD28 pathway is important for superantigenic stimulation of T cells and that signaling through this pathway can substitute for the APC-associated costimulatory activity that is essential for T cell stimulation. Moreover, the results are consistent with the notion that, in the presence of appropriate costimulation, pep M5 can directly interact with T cells and induce them to proliferate.