Heat-stable antigen is an important costimulatory molecule on epidermal Langerhans' cells.
Heat-stable antigen (HSA), expressed by activated B cells, has been described as a costimulatory molecule for CD4+ T cells. Because epidermal Langerhans cells (LC) are known to express HSA, we determined whether LC HSA also served as a costimulator of Th cells. We have confirmed that HSA is expressed by freshly prepared (fresh) and, to a lesser extent, short-term cultured (cultured) LC and we demonstrate that costimulatory effects of HSA are prominent on fresh and 1-day cultured LC, whereas 2- to 4-day cultured LC exhibit less HSA-costimulatory activity. The anti-HSA mAb 20C9 almost completely blocked the proliferative response of Th1 or lymph node T cells induced by fresh or cultured LC. 20C9 also specifically inhibited LC-dependent IL-2 production by Th1 cells. The inhibitory effect of 20C9 was not observed when Th2 cells were substituted for Th1 cells or peripheral lymph node T cells. Furthermore, Th1 cells rescued from cocultures of T cells and 20C9-treated, Ag-pulsed LC, (but not from control-treated cocultures) were anergic to restimulation with untreated Ag-pulsed LC. These data suggest that LC HSA is an important costimulatory molecule in Th1 cell-dependent cutaneous immune reactions.
Enk
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Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Katz
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D051927:CD24 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy; D004817:Epidermis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase