Monocyte-dependent regulation of T lymphocyte activation through CD98

CD98 is a 125 kDa heterodimer, which is strongly expressed on the surface of activated and proliferating cells, Its expression is strikingly regulated during T cell differentiation and activation, but the role of CD98 during T lymphocyte responses is not yet understood, We report here that proliferation of resting peripheral blood mononuclear cells (PBMC) induced by lectin, superantigen (SAg) or conventional antigens was blocked by anti-CD98 heavy chain (CD98hc) mAb, In contrast, anti-CD98hc did not block responses of T cell clones or lines, Anti-CD98hc inhibited IL-2 receptor expression and progression of T cells from G(1) to S phase, but did not reduce expression of the IL-2 gene. Anti-CD98hc mAb did not regulate the initial activation events involving the TCR and co-receptor structures, but instead inhibited T lymphocyte responses even when added 18 h or more after the activation stimulus, Further experiments demonstrated that anti-CD98 was not directly affecting T cells in this system, but was instead acting on accessory cells, This was supported using a novel xenogeneic system that takes advantage of the lack of xenoreactivity of purified human T cells against mouse splenocytes, Despite absence of a direct xenoresponse to murine spleen cells, human T cells were activated by SAg presented by murine splenic antigen-presenting cells (APC), Murine anti-human CD98hc did not block T cell proliferation in this system, Furthermore, responses using monocyte-depleted PBMC as APC were not blocked by anti-CD98hc, Taken together, the present data suggests that triggering of human monocyte CD98 can suppress T cell proliferation by a process that halts progression through the cell cycle of recently activated T lymphocytes, This may represent a novel pathway for monocyte regulation of T cell activation.