Differentiation of resting human peripheral blood gamma delta T cells toward Th1- or Th2-phenotype.
Depending on the microenvironment, murine gamma delta T cells differentiate into either Th1 (IFN-gamma-producing) or Th2 (IL-4-producing) cells. It is unclear, however, whether circulating human peripheral blood gamma delta T cells can be driven into Th1 or Th2 cells by modulation of the priming cytokine milieu. In this study, peripheral blood gamma delta T cells were stimulated by phosphoantigen (isopentenyl pyrophosphate) or Daudi lymphoma cells in the presence of Th1-priming (rIL-12, anti-IL-4 Ab) or Th2-priming (rIL-4, anti-IL-12 Ab) conditions. Single-cell analysis of cytokine secretion (IFN-gamma and IL-4) was performed by flow cytometry after 18 h and after restimulation of expanded gamma delta T cells. The early activation of resting gamma delta T cells was characterized by the induction of IFN-gamma. Priming under Th1 conditions induced a Th1 profile characterized by increased secretion of IFN-gamma and TNF-alpha, while Th2 conditions caused increased production of IL-4 (Th2 profile) by the gamma delta T cells. These results indicate that the major subset of human gamma delta T cells can be polarized into either Th1 or Th2 cytokine pattern depending on the cytokine milieu in which contact with antigen occurs.
Wesch
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Institute of Immunology, University Hospital Kiel, D-24105 Kiel, Germany.
Glatzel
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Kabelitz
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D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000941:Antigens / Q000276:immunology; D002051:Burkitt Lymphoma / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D005434:Flow Cytometry; D045782:Hemiterpenes; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D009943:Organophosphorus Compounds / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology*; D018418:Th2 Cells / Q000166:cytology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000941:Antigens; D045782:Hemiterpenes; D007375:Interleukin-1; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D018664:Interleukin-12; D015847:Interleukin-4; C004809:isopentenyl pyrophosphate; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate