Differential effects of type I IFNs on the growth of WC1- CD8+ gamma delta T cells and WC1+ CD8- gamma delta T cells in vitro.
Type I IFNs have a broad array of immunoregulatory functions that include up-regulation of type 1 immune responses through enhancing differentiation and activation of CD8+ T cells and CD4+ Th1 cells. Ovine trophoblast IFN-tau is a recently described type I IFN with the potential for therapeutic use, based on its potent antiviral activity yet low toxicity. Studies were designed to determine the immunoregulatory effects of IFN-tau on Ag-stimulated T cells, and a novel effect of type I IFNs on gammadelta T cells was observed. In cultures of parasite Ag-stimulated bovine T cells that contained a mixture of alphabeta and gammadelta T cells, both IFN-tau and IFN-alpha suppressed the expansion of WC1+ CD2- CD6- CD8- gammadelta T cells, yet stimulated the growth of WC1- CD2+ CD6+ CD8+ gammadelta T cells and CD8+ alphabeta T cells. The CD8+ gammadelta T cell subset expressed high levels of the IL-2R alpha-chain. Furthermore, we showed that type I IFN enhanced IL-2 production by these Ag-stimulated T cell lines. In short term cultures of PBMC, IL-2 stimulated an expansion of WC1- CD6+ CD8+ gammadelta T cells, which was significantly increased by IFN-tau, even though IFN-tau alone did not support cell survival. These studies demonstrate for the first time that type I IFNs differentially modulate the proliferation of different subsets of gammadelta T cells, which appears to act in part via IL-2.
Tuo
W
W
Department of Veterinary Pathology and Microbiology, Washington State University, Pullman 99164, USA.
Bazer
F W
FW
Davis
W C
WC
Zhu
D
D
Brown
W C
WC
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000097:blood; D012756:Sheep; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D006133:Growth Substances; D007370:Interferon Type I; D016898:Interferon-alpha; D007376:Interleukin-2; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma