Immunoregulatory roles of adhesive interactions between lymphocytes and gingival fibroblasts

Abstract

Chronic adult periodontitis is usually characterized by inflammatory cell accumulation in the extravascular periodontal connective tissue. In order to reveal how the lymphocyte migration and retention in periodontal lesions is regulated, we have focused on the molecular basis for the adhesive interactions between lymphocytes and human gingival fibroblasts (HGF). In this study, we investigated the involvement of cell adhesion molecules in adhesive interactions between lymphocytes and HGF. We found that activated lymphocytes bound strongly to HGF and VLA integrins, extracellular matrix receptors, play crucial roles in the binding. Interestingly, we first revealed that CD44 molecules (hyaluronate receptor) on lymphocytes also participated in lymphocyte-HGF interactions and that hyaluronate anchored on the surface of HGF functioned as the ligand for CD44. In addition, when HGF were stimulated with inflammatory cytokines such as IL-1, TNF alpha and IFN gamma, the binding avidity between lymphocytes and HGF was significantly increased and the adhesion was mainly mediated by LFA-1/ICAM-1 pathway. We then examined the possibility whether lymphocyte-HGF interaction may cause activation of HGF. When HGF directly interacted with lymphocytes for 3 h, IL-1 beta mRNA expression was clearly increased in HGF. These findings suggested that the adhesive interactions between lymphocytes and HGF was mediated at least by VLA integrins, LFA-1/ICAM-1 and CD44/hyaluronate and that the heterotypic cell-cell interactions could mutually cause intracellular signal transduction.

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.…”

“…This raised the possibility that the adhesive interactions may provide a certain intracellular signal and mutually affect each cellular function through the adhesive interactions As has been described above, it was demonstrated that IFN-ystimulated fibroblasts can function as APC under specific conditions by physically interacting with T-lymphocytes (Geppert and Lipsky, 1985;Maurer et al, 1985Maurer et al, , 1987Pober et al, 1983;Shimabukuro et at., 1996). On the other hand, it was also observed that the IFN-y-stimulated HGF suppressed the primary proliferative responses induced by mitogen or allo-APC and that the suppression was also caused by a direct adherence of T-lymphocytes to IFN-ystimulated HGF (Shimabukuro et al, 1992) (Murakami et al, 1996a(Murakami et al, , 1997 (Wilson et ca1., 1994). The fact that ICE mRNA expression was also detected in both resting and cytokine-activated HGF (Murakami et al, 1997) have an ability to produce the mature form of IL-IP.…”

“…On the other hand, it was also observed that the IFN-y-stimulated HGF suppressed the primary proliferative responses induced by mitogen or allo-APC and that the suppression was also caused by a direct adherence of T-lymphocytes to IFN-ystimulated HGF (Shimabukuro et al, 1992) (Murakami et al, 1996a(Murakami et al, , 1997 (Wilson et ca1., 1994). The fact that ICE mRNA expression was also detected in both resting and cytokine-activated HGF (Murakami et al, 1997) have an ability to produce the mature form of IL-IP.…”

“…In a series of studies, we showed that cytokine-activated HGF increased the binding avidity for T-lymphocytes (Murakami et al, 1997). Although adhesion between T-lymphocytes and resting HGF was not effectively inhibited by anti-ICAM-l or anti-LFA-1 mAb, the increased binding between T-lymphocytes and cytokine-activated HGF was significantly inhibited by anti-ICAM-1 or anti-LFA-1 mAbs (Murakami et al, 1997), suggesting that LFA-1 and its ligand, ICAM-1, were also involved in T-lymphocyte-HGF interaction. As described above, it was reported that the LFA-1/ICAM-l pathway plays a major role in T-lymphocyte-dermal fibroblast adherence.…”

Adhesion and transcellular migration of neutrophils and B lymphocytes on fibroblasts

“…It is likely that leukocytes interact directly with cardiac fibroblasts. Indeed, there are several examples in the literature of interactions between leukocytes and fibroblasts of different origins [5][6][7][8][9][10][11][12][13][14][15]. These interactions appear to modulate the level of subsequent fibrosis and might also affect the degree of inflammation in those tissues.…”