Synovial microenvironment‐t cell interactions

Abstract

Synovitis in rheumatoid arthritis is characterized by infiltration of the synovium by T and B lymphocytes and monocytes, as well as by the proliferation of synovial lining cells, fibroblasts, and endothelial cells. To study synovial cell‐T cell interactions in vitro, we established cultures of fibroblast‐like synovial cells, and used these cells in a synovial cell‐T cell binding assay. Using T cells at various stages of differentiation and activation, we found that human thymocytes and mitogen‐activated peripheral blood T cells bound to fibroblast‐like synovial cells, whereas fresh peripheral blood T cells did not. Moreover, activated T cells from inflammatory synovial tissue or from synovial fluid also bound to fibroblast‐like synovial cells cultured in vivo. Antibodies against certain epitopes of the T cell CD2 (35.1) and synovial cell lymphocyte function‐associated antigen‐3 (LFA‐3) (TS2/9) molecules inhibited synovial cell‐thymocyte binding. However, these same anti‐CD2 and anti‐LFA‐3 antibodies only partially inhibited synovial cell binding to activated normal peripheral blood T cells. Moreover, T cells from inflammatory synovium from rheumatoid arthritis and psoriatic arthritis patients also bound to synovial cells in vitro. These findings demonstrate that fibroblast‐like synovial cells are capable of binding to human T cells in vitro, and suggest that during the course of inflammatory synovitis, synovial fibroblast‐T cell interactions may occur in vivo.

Direct Contact between T Lymphocytes and Human Dermal Fibroblasts or Synoviocytes Down-regulates Types I and III Collagen Production via Cell-associated Cytokines

“…In vitro studies revealed that human T cells have the ability to adhere to synoviocytes as well as to dermal fibroblasts via CD2/CD58 (LFA-3) and LFA-1 (CD11a/CD18)/CD54 (ICAM-1) interactions (12,13,49). Furthermore, the cellular adhesion between T cells and synoviocytes induces the production of IL-1␤ by synovial cells in part through LFA-1-ICAM-1 interaction (17).…”

Lymphocyte-Fibroblast Interactions

“…B-lymphocytes can be activated not only by various cytokines but also by direct interactions with T-lymphocytes via TCR/MHC class 11 and gp39/CD40 interactions (Noell et al, 1992;laneway and Trevers, 1994). On the other hand, several lines of evidence have demonstrated that the interaction of lymphocytes with other cell types is also an important component of inflammatory responses and is essential in a number of other contact-mediated processes, such as lymphopoiesis and lymphocyte homing and migration (Dustin and Springer, 1988;Haynes et al, 1988;Denning et al, 1989;Berg et al, 1991;van Ewi jk, 1991;Kincade et al, 1993;De Boer et al, 1994;Downey, 1994).…”

“…Piela and Korn (1990) reported that the increased adhesion between IFN-y-stimulated dermal fibroblast and resting T-lymphocytes was inhibited by mAb to ICAM-1 or LFA-1 and concluded that the ICAM-1/LFA-l pathway plays a major role in their system. Alternatively, it was proposed that T-lymphocyte adhesion to human synovial fibroblasts resulted in cellular retention in the inflamed synovium (Haynes et al, 1988;Krzesicki et al, 1991 (Murakami et al, 1993a,b). VLA integrins are members of the 11 subfamily, and each contains the 11 subunit in association with one of at least six distinct (x subunits (Hemler, 1990 (Murakami et al, 1993a).…”

The accumulation of inflammatory cells in synovial sheath and epitenon during adhesion formation in healing rat flexor tendons

“…Isolation and activation of T lymphocytes Thymocytes were teased from thymus obtained from four control rats, aged 3-5 months, and were purified as described [14]. Activated T lymphocytes were prepared by the incubation of thymocytes with RPMI 1640 medium (GIBCO) supplemented with 10% fetal calf serum (FCS) and 20 pg/ml concanavalin A (Con A; Sigma) for 3 days, and were then washed with 0 3 M amethylmannoside (Sigma) to remove residual Con A [14].…”

“…Activated T lymphocytes were prepared by the incubation of thymocytes with RPMI 1640 medium (GIBCO) supplemented with 10% fetal calf serum (FCS) and 20 pg/ml concanavalin A (Con A; Sigma) for 3 days, and were then washed with 0 3 M amethylmannoside (Sigma) to remove residual Con A [14]. Activated T lymphocytes were selected using plastic surfaces coated with anti-CD8 antibodies [15].…”