Abstract
T cell activation requires engagement of the T cell receptor (TCR) with an immunogenic peptide bound to a major histocompatibility complex (MHC) molecule and a costimulatory signal provided by the antigen-presenting cell (APC). Although these events result in T cell clonal expansion, ligation of the TCR alone (lack of a costimulatory signal) does not stimulate T cell activation, but rather results in unresponsiveness known as T cell anergy. Most investigations of the T cell activation mechanism have focussed on the system consisting of classical APC and T cells, but it is known that T cell can coexpress not only the adhesion molecules that provide costimulatory signals to T cells, but also their counter-receptors. In this paper, we analyze the role of adhesion molecules in T cell activation using a mouse CD4+ T cell clone, DB14. DB14 cells were able to proliferate upon stimulation of the TCR/CD3 complex alone either by appropriate MHC class II cDNA transfected CHO cells plus peptides or anti-CD3 monoclonal antibodies (mAb). Moreover the magnitude of anti-CD3 mAb-induced T cell proliferation was dependent on cell density, suggesting that cell to cell contact is important for the anti-CD3 mAb-induced DB cell proliferation. The DB14 cell expressed B7-1, CD28, ICAM-1 and LFA-1 molecules on its cell surface. Importantly, anti-CD3 mAb-induced proliferation was inhibited by CTLA-4 Ig or anti-LFA-1 mAb and the inhibitory effect of anti-LFA-1 mAb was stronger than that of CTLA-4 Ig. These results suggest that DB14 cells require two signals, the first, a TCR-mediated signal by anti-CD3 mAb and the ?second, a costimulatory signal through interaction of B7/CD28 and LFA-1/ICAM-1 pathways. Thus adhesion molecules on DB14 cells can provide a costimulatory signal for T cell proliferation, which suggests that T cells may provide costimulatory signals to each other at inflamed regions in vivo.
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