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

Abstract

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.

The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function

“…In the same way as Cat K, a proportion of CatL is physiologically secreted and can be extracellularly activated (76) after which it can process several ECM proteins, such as fibronectin, laminin, elastin, and collagen types I, IV, and XVII (76,77,(105)(106)(107). Furthermore, ECM components have been shown to transduce survival signals (108) and promote the proliferation of lymphocytes by signalling through integrins (109). By regulating the level of expression of ECM components in lymphoid organs, CatL can have a broad effect on immune system (104).…”

Cathepsin-L Influences the Expression of Extracellular Matrix in Lymphoid Organs and Plays a Role in the Regulation of Thymic Output and of Peripheral T Cell Number

“…It has also been demonstrated that ECM components promote the proliferation of T cells by signaling through integrins (9). Besides, different growth factors, chemokines and hormones have been shown to be associated with ECM (10 -13), this association being an important factor in regulating not only their availability but also the cellular responsiveness (10,(12)(13)(14).…”