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Involvement of fibronectin and its receptor in human lymphocyte proliferation
1Terry Fox Laboratory, University of British Columbia, Vancouver, Canada.
Abstract:
Adhesion between lymphocytes and antigen-presenting cells is necessary for the development of certain immune reactions. We have previously shown that fibronectin (FN) added to mixed lymphocyte cultures (MLC) can restore a decreased lymphocyte proliferation in immunocompromised individuals. Using highly purified cell populations from peripheral blood for depletion and adding back experiments we show here that exogenous FN enhanced proliferation only when allogeneic monocytes were co-cultured with responder lymphocytes. Although lymphocyte proliferation in MLC was augmented by FN, there was no preferential proliferation of any particular major lymphocyte subpopulation in cultures supplemented with FN as compared to control cultures lacking its addition. Antibody against the FN receptor (FN-R) of the beta 1 integrin family, as well as Arg-Gly-Asp containing peptide, could inhibit alloantigen-induced lymphocyte proliferation in a concentration-dependent manner. Anti-CD3-induced proliferation was inhibited by anti-FN-R antibody but not Arg-Gly-Asp peptide whereas no inhibition was seen with the phytohemagglutinin (PHA)-induced lymphocyte proliferation. This study presents further evidence that FN and its receptor (alpha 5 beta 1) are involved in the augmentation of T-cell responsiveness to proliferative stimuli.