Abstract
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.
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Abbreviations
- TNF-α:
-
tumor necrosis factor-α
- IFN-γ:
-
interferon-γ
- GM-CSF:
-
granulocyte macrophage-colony-stimulating factor
- AICD:
-
activation-induced cell death
- Th1:
-
type 1 helper T cell
- Th2:
-
type 2 helper T cell
- ThGM:
-
GM-CSF-secreting helper T cell
- Tc1:
-
type 1 cytotoxic T cell
- Tc2:
-
type 2 cytotoxic T cell
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Acknowledgements
This work was supported in part by USPHS grants (AI43384, AI057596, DE014913, DE019932, and GM866889), the Ministry of Science and Technology of China (2010CB945600), and the National Science and Technology Project of China (2009ZX09503-024).
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Zhang, J., Roberts, A., Liu, C. et al. A novel subset of helper T cells promotes immune responses by secreting GM-CSF. Cell Death Differ 20, 1731–1741 (2013). https://doi.org/10.1038/cdd.2013.130
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DOI: https://doi.org/10.1038/cdd.2013.130
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