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  • Title: Failure of correlation between B7 expression and activation of interleukin-2-secreting T cells.
    Author: Lombardi G, Sidhu S, Dodi T, Batchelor R, Lechler R.
    Journal: Eur J Immunol; 1994 Mar; 24(3):523-30. PubMed ID: 7510233.
    Abstract:
    It 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 costimulation 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 is currently under investigation.
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