6533b830fe1ef96bd12967c7

RESEARCH PRODUCT

Modulation of proliferation and lymphokine secretion of murine CD4+ T cells and cloned Th1 cells by proteins of the extracellular matrix.

subject

description

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 Th1 clone cells, activated by immobilized anti-CD3 mAb. ECM proteins used in various concentrations had no effect on IL-2 production or proliferation of highly purified CD4+ T cell populations. 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 level of proliferation attainable by added irradiated splenocytes was not reached. Using Th1 cell clone M4, enhanced production of IL-2 in the presence of immobilized ECM proteins was observed. At a submitogenic anti-CD3 mAb dose, proliferation of M4 T cells was augmented by the ECM proteins in a concentration range that optimally induced IL-2 production. IL-2R p55 was up-regulated on M4 T cells by collagen type IV and fibronectin to the same level that was induced by exogenously added IL-2, whereas added accessory cells induced a higher level of IL-2R p55 expression. Likewise, in dot-blot analysis a comparable quantity of IL-2R p55- and p75-specific transcripts was induced by collagen type IV or fibronectin and by IL-2, which was lower than that induced by antigen-presenting cells. Our data suggest that the enhanced proliferation of M4 T cells induced by ECM proteins is not the consequence of direct up-regulation of IL-2R, but appears to be due indirectly to elevated secretion of IL-2. At an optimal anti-CD3 mAb dose the collagens inhibited M4 T cell proliferation. Diminished cell surface expression of IL-2R p55 following stimulation with anti-CD3 mAb plus collagen type IV compared with anti-CD3 mAb alone was observed and may be responsible for growth inhibition.