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.