title: 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.
authors.affiliation: Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Tschoetschel
authors.forename: J
authors.initials: J
authors.lastname: Schwing
authors.forename: S
authors.initials: S
authors.lastname: Frosch
authors.forename: E
authors.initials: E
authors.lastname: Schmitt
authors.forename: D
authors.initials: D
authors.lastname: Schuppan
authors.forename: A B
authors.initials: AB
authors.lastname: Reske-Kunz
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D002999:Clone Cells; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D019012:Integrin beta1 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D008222:Lymphokines; D015375:Receptors, Interleukin-2