Costimulatory signals can selectively modulate cytokine production by subsets of CD4+ T cells.
Analysis of experimental animal models and human clinical samples has indicated that the selective activation of CD4+ T cell subsets with distinct profiles of cytokine production plays an important role in the pathogenesis of human inflammatory and allergic diseases. The possibility that differential activation of costimulatory pathways is a mechanism for selectively modulating cytokine production by CD4+ T cells was tested. The proliferative response and cytokines secreted by a panel of human CD4+ T cell clones, representative of Th1 or Th2/0 cells, in response to activation of different costimulatory pathways was measured. CD28-mediated costimulatory signals induced proliferation and IFN-gamma secretion by Th1 cells. Although CD28-ligation induced Th2/0 cells to proliferate, it did not trigger IL-4 production. Ligation of LFA-1 and CD45 isoforms also generated costimulatory signals activating cytokine secretion by the different types of T cell clones. Th1 cells secreted the same profile of cytokines, irrespective of which costimulatory pathway was engaged. However, the cytokine secreted by a subset of Th2/0 cells varied, depending upon which costimulatory pathways were activated. These results suggest that the costimulatory pathways activated by APCs can selectively influence cytokine production by CD4+ T cell subsets.
Department of Leukocyte Biology, Syntex Research, Palo Alto, CA 94303.
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Shanafelt
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Soderberg
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Allsup
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Adelman
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Peltz
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Lahesmaa
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002415:Cats; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008193:Lyme Disease / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D008925:Mites; D015398:Signal Transduction; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
D018106:CD28 Antigens; D017252:CD3 Complex; D008222:Lymphokines; D015847:Interleukin-4; D007371:Interferon-gamma