A novel subset of helper T cells promotes immune responses by secreting GM-CSF.
Helper T cells are crucial for maintaining proper immune responses. Yet, they have an undefined relationship with one of the most potent immune stimulatory cytokines, granulocyte macrophage-colony-stimulating factor (GM-CSF). By depleting major cytokines during the differentiation of CD4(+) T cells in vitro, we derived cells that were found to produce large amounts of GM-CSF, but little of the cytokines produced by other helper T subsets. By their secretion of GM-CSF, this novel subset of helper T cells (which we have termed ThGM cells) promoted the production of cytokines by other T-cell subtypes, including type 1 helper T cell (Th1), type 2 helper T cell (Th2), type 1 cytotoxic T cell (Tc1), type 2 cytotoxic T cell (Tc2), and naive T cells, as evidenced by the fact that antibody neutralization of GM-CSF abolished this effect. ThGM cells were found to be highly prone to activation-induced cell death (AICD). Inhibitors of TRAIL or granzymes could not block AICD in ThGM cells, whereas inhibition of FasL/Fas interaction partially rescued ThGM cells from AICD. Thus, ThGM cells are a novel subpopulation of T helper cells that produce abundant GM-CSF, exhibit exquisite susceptibility to apoptosis, and therefore play a pivotal role in the regulation of the early stages of immune responses.
1] Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA [2] Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA.
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Zhang
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Roberts
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Liu
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Ren
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Xu
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Zhang
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Devadas
Yufang
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Shi
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D003564:Cytidine Deaminase / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D007109:Immunity / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase