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.