MODULATION OF PROLIFERATION AND LYMPHOKINE SECRETION OF MURINE CD4(-CELLS AND CLONED T(H)1 CELLS BY PROTEINS OF THE EXTRACELLULAR-MATRIX() T)

In this study we investigated the co-stimulatory signaling capacity of diverse proteins of the extracellular matrix (ECM) for murine resting CD4(+) T cells and T(h)1 clone cells, activated by immobilized anti-C D3 mAb, ECM proteins used in various concentrations had no effect on I L-2 production or proliferation of highly purified CD4(+) T cell popul ations, When the preparation of CD4(+) T cells contained contaminating accessory cells, IL-2 secretion and proliferation was enhanced in the presence of co-immobilized collagens or fibronectin, However, the lev el of proliferation attainable by added irradiated splenocytes was not reached, Using T(h)1 cell clone M4, enhanced production of IL-2 in th e presence of immobilized ECM proteins was observed, At a submitogenic anti-CD3 mAb dose, proliferation of M4 T cells was augmented by the E CM proteins in a concentration range that optimally induced IL-2 produ ction, IL-2R p55 was up-regulated on M4 T cells by collagen type IV an d fibronectin to the same level that was induced by exogenously added IL-2, whereas added accessory cells induced a higher level of IL-2R p5 5 expression, Likewise, in dot-blot analysis a comparable quantity of IL-2R p55- and p75-specific transcripts was induced by collagen type I V or fibronectin and by IL-2, which was lower than that induced by ant igen-presenting cells, Our data suggest that the enhanced proliferatio n of M4 T cells induced by ECM proteins is not the consequence of dire ct up-regulation of IL-2R, but appears to be due indirectly to elevate d secretion of IL-2, At an optimal anti-CD3 mAb dose the collagens inh ibited M4 T cell proliferation, Diminished cell surface expression of IL-2R p55 following stimulation with anti-CD3 mAb plus collagen type I V compared with anti-CD3 mAb alone was observed and may be responsible for growth inhibition.