CD44-Hyaluronate Interaction Participates in the Adherence of T-lymphocytes to Gingival Fibroblasts

Abstract

It has already been clarified that peripheral blood T-lymphocytes which had been activated with phorbol 12-myristate 13-acetate (PMA) acquired the ability to bind to human gingival fibroblasts (HGF) and that the adherence was mediated by VLA integrins. However, these studies also raised the possibility that molecules other than VLA integrins should be involved in the adherence between T-lymphocytes and HGF. In this study, the possible involvement of CD44, a hyaluronate receptor, in heterotypic cell-cell interactions was investigated. It was confirmed that PMA-activated T-lymphocytes strongly adhered to plate-coated hyaluronate and that the hyaluronate binding was clearly inhibited by the addition of OS/37, a newly established mAb specific for the hyaluronate-binding epitope on CD44. Interestingly, OS/37 also blocked the HGF binding of the activated T-lymphocytes when the adherence to HGF was assessed at 4 degrees C, at which temperature the adhesion of integrin molecules diminished, while that of CD44 functioned normally. Immunofluorescence staining revealed that hyaluronate was anchored along the cell surface of HGF. Furthermore, the binding of activated T-lymphocytes to HGF was significantly inhibited by the treatment of HGF with hyaluronidase. These results clearly demonstrated that CD44-hyaluronate interactions participated at least in part in the adhesiveness of T-lymphocytes to HGF.

Lymphocyte-Fibroblast Interactions

“…A mAb OS/37, which is specific for a HA-binding epitope on CD44, was utilized to examine the possible involvement of CD44/HA interaction in T-lymphocyte-HGF adherence. It was found that OS/37 inhibited the binding of T-lymphocytes to HGF, while treatment of HGF with hyaluronidase likewise abrogated the binding in a dose-dependent manner (Murakami et al, 1996b(Murakami et al, , 1997. These results suggest that the CD44/HA pathway also participates in T-lymphocyte-HGF adherence.…”

“…On the other hand, lymphocytes express a variety of ECM receptors which function as cell adhesion molecules and are strictly regulated by various stimuli (Dustin and Springer, 1988;Hynes, 1987;Lesley et al, 1990;Murakami et al, 1990Murakami et al, , 1991bMurakami et al, , 1993aMurakami et al, , 1994 (Aruffo et al, 1990;Jalkanen and lalkanen, 1992;Lesley et al, 1993), and that activated lymphocytes, which demonstrated binding ability to HGF, also bound to HA via CD44 (Murakami et al, 1994). In addition, confocal laser scanning micrographs utilizing a Texas Red-labeled HA-binding peptide revealed that HA was anchored on the cell surface of HGF (Murakami et a!., 1996b). Thus, it is possible that CD44-HA interaction may participate in lymphocyte-HGF adhesion.…”

Involvement of T-Lymphocytes in Periodontal Disease and in Direct and Indirect Induction of Bone Resorption

“…The involvement of integrins in the lymphocyte migration into gingival tissues was demonstrated by the increased number of mononuclear cells, which express oc4 and a6 integrins (Del Castillo et al, 1996), and T-cells, which express LFA-1 (Takeuchi et al, 1995) in periodontally diseased gingival tissue. Lymphocytes also appear to adhere to gingival fibroblasts by means of CD44/hyaluronate, LFA-1/ICAM-1, VLA-4, and VLA-5 (Murakami et al, 1993(Murakami et al, , 1996, suggesting that lymphocyte retention in the gingival tissue, by adhering to fibroblasts, may influence inflammation (Murakami and Okada, 1997 (Sallusto et al, 2000). Several studies have demonstrated the production of chemokines in gingival tissue (Yu et al, 1993;Yu and Graves, 1995;Zehnder et al, 1999).…”

Human Gingival Fibroblasts Rescue Butyric Acid-Induced T-Cell Apoptosis

“…In inflamed periodontal lesions, dense lymphocytic infiltrations are usually observed in the extravascular periodontal connective tissue, adjacent to gingival fibroblasts. Previous studies revealed that activated lymphocytes can adhere to gingival fibroblasts in vitro (20,21), and that direct interactions between gingival fibroblasts and lymphoid cells induce the expression of mRNA for proinflammatory cytokines in gingival fibroblasts (22). Other reports indicate that various bacterial products-such as LPS, fimbriae, and proteases (37); interleukin 17 (IL-17) produced by T lymphocytes (18); and IL-18 in synovial fluids (19)-directly affect cytokine production by gingival fibroblasts.…”