AbstractIt is well established that triggering interleukin‐2 (IL‐2) secretion by helper T cells requires the T cell to receive at least two discrete signals. One signal is transduced by the CD3 complex, usually as the result of T cell receptor (TcR) occupancy, the second, or co‐stimulatory, signal involves a non‐cognate interaction between cell surface accessory molecules on the antigen‐presenting cell (APC) and the T cell. A molecular interaction that has been implicated in the provision of co‐stimulatory signals is that between B7/BB1 on the APC and its ligands, CD28 and CTL‐A4 on the T cell.We have studied the ability of HLA‐class II antigen‐positive human T cells and a population of DR1‐expressing transfected human fibroblasts to stimulate a proliferative response by human T cell clones, and by freshly isolated peripheral blood T cells. Despite their high levels of B7 expression, the T cell clones, were unable to induce proliferation or IL‐2 secretion by DR‐restricted, antigen‐specific T cells. In contrast, the DR1‐expressing transfectants, that were B7 negative, induced a strong proliferative response. When these two populations of DR‐expressing cells were used to stimulate a primary alloresponse the results were reversed, in that the T cell clones induced a strong alloresponse but the transfected fibroblasts induced no proliferation.These results suggest that the expression of B7 may be necessary for co‐stimulation of unprimed T cells, but not of established T cell clones. Furthermore the data show that the expression of B7 by an APC does not necessarily lead to IL‐2 production or protection from the induction of tolerance. The mechanisms responsible for the inability of these T cells to provide full activation signals when used as APC
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