T CELL-VASCULAR SMOOTH-MUSCLE CELL-INTERACTIONS - ANTIGEN-SPECIFIC ACTIVATION AND CELL-CYCLE BLOCKADE OF T-HELPER CLONES BY CLONED VASCULARSMOOTH-MUSCLE CELLS

Histological observations have demonstrated the presence of T lymphocy tes in atherosclerotic plaques, often in close association with vascul ar smooth muscle cells (VSMC). We have examined the interaction occurr ing between cloned murine VSMC and histocompatibility-matched, antigen -specific Th1 and Th2 cell lines. Incubation of either Th1 or Th2 cell s with antigen-pulsed VSMC resulted in the formation of T cell-VSMC co njugates accompanied by morphological changes in both cell types, This interaction resulted in an antigen-dependent activation of IL-2 recep tor expression by the Th cells, demonstrating the ability of cloned VS MC to process and present antigen through the exogenous pathway. Howev er, although the T cells were activated to express IL-2 receptors by a ntigen-pulsed VSMC, they were unable to progress through cell cycle, T he secretion of an inhibitory mediator by VSMC was suggested by the ob servations that (1) fixation of the VSMC's eliminated the inhibitory s ignal and (2) the supernatants of IFN gamma-primed VSMC displayed simi lar inhibitory activity. The inhibitory effect could not be abrogated with indomethacin or an inhibitor of the generation of reactive nitrog en intermediates, indicating that prostaglandin synthesis and/or nitri c oxide production are not solely responsible for the inhibition of pr oliferation. Flow cytometric cell cycle analysis revealed that VSMC de livered signals resulting in a late G1 blockade of T cell cycle progre ssion. Mitogen responses of purified primary T cells are also dramatic ally inhibited by IFN gamma-treated VSMC, despite significant IL-2 pro duction, Our data depict a complex and intimate T cell-VSMC interactio n and suggest that mutual activation events may occur. (C) 1995 Academ ic Press, Inc.