T cell--vascular smooth muscle cell interactions: antigen-specific activation and cell cycle blockade of T helper clones by cloned vascular smooth muscle cells.
Histological observations have demonstrated the presence of T lymphocytes in atherosclerotic plaques, often in close association with vascular smooth muscle cells (VSMC). We have examined the interaction occurring between cloned murine VSMC and histocompatibility-matched, antigen-specific Th1 and Th2 cell lines. Incubation of either Th1 or Th2 cells with antigen-pulsed VSMC resulted in the formation of T cell-VSMC conjugates accompanied by morphological changes in both cell types. This interaction resulted in an antigen-dependent activation of IL-2 receptor expression by the Th cells, demonstrating the ability of cloned VSMC to process and present antigen through the exogenous pathway. However, although the T cells were activated to express IL-2 receptors by antigen-pulsed VSMC, they were unable to progress through cell cycle. The secretion of an inhibitory mediator by VSMC was suggested by the observations that (1) fixation of the VSMC's eliminated the inhibitory signal and (2) the supernatants of IFN gamma-primed VSMC displayed similar inhibitory activity. The inhibitory effect could not be abrogated with indomethacin or an inhibitor of the generation of reactive nitrogen intermediates, indicating that prostaglandin synthesis and/or nitric oxide production are not solely responsible for the inhibition of proliferation. Flow cytometric cell cycle analysis revealed that VSMC delivered signals resulting in a late G1 blockade of T cell cycle progression. Mitogen responses of purified primary T cells are also dramatically inhibited by IFN gamma-treated VSMC, despite significant IL-2 production. Our data depict a complex and intimate T cell-VSMC interaction and suggest that mutual activation events may occur.
Suttles
J
J
Department of Biochemistry, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA.
Miller
R W
RW
Moyer
C F
CF
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002450:Cell Communication; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis; D005434:Flow Cytometry; D015870:Gene Expression; D006650:Histocompatibility Testing; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma; D004247:DNA; D013936:Thymidine