NK1.1^- CD4⁺ NKG2D⁺ T cells suppress DSS-induced colitis in mice through production of TGF-β.

CD4⁺ NKG2D⁺ T cells are associated with tumour, infection and autoimmune diseases. Some CD4⁺ NKG2D⁺ T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-β and FasL to facilitate tumour evasion. Here, murine CD4⁺ NKG2D⁺ T cells were further classified into NK1.1^- CD4⁺ NKG2D⁺ and NK1.1⁺ CD4⁺ NKG2D⁺ subpopulations. The frequency of NK1.1^- CD4⁺ NKG2D⁺ cells decreased in inflamed colons, whereas more NK1.1⁺ CD4⁺ NKG2D⁺ cells infiltrated into colons of mice with DSS-induced colitis. NK1.1^- CD4⁺ NKG2D⁺ cells expressed TGF-β and FasL without secreting IFN-γ, IL-21 and IL-17 and displayed no cytotoxicity. The adoptive transfer of NK1.1^- CD4⁺ NKG2D⁺ cells suppressed DSS-induced colitis largely dependent on TGF-β. NK1.1^- CD4⁺ NKG2D⁺ cells did not expressed Foxp3, CD223 (LAG-3) and GITR. The subpopulation was distinct from NK1.1⁺ CD4⁺ NKG2D⁺ cells in terms of surface markers and RNA transcription. NK1.1^- CD4⁺ NKG2D⁺ cells also differed from Th2 or Th17 cells because the former did not express GATA-3 and ROR-γt. Thus, NK1.1^- CD4⁺ NKG2D⁺ cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.

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