Defining a novel subset of CD1d-dependent type II natural killer T cells using natural killer cell-associated markers.

ABSTRACT: Natural killer T (NKT) cells are ?? T cell receptor (TCR) expressing innate-like T cells that display natural killer (NK) cell markers. Based on TCR characteristics, they are divided into two groups restricted to the MHC class I-like molecule CD1d. Type I NKT cells, most extensively studied, are identified by a semi-invariant V?14-J?18 (mouse, V?24-J?18 in humans) TCR reactive to the prototypic ligand ?-galactosylceramide presented on CD1d. In contrast, type II NKT cells display diverse TCR reacting to different CD1d-presented ligands. There are no reagents that identify all type II NKT cells, limiting their exploration. Here, we searched for novel type II NKT cells by comparing J?18^-/- MHCII^-/- mice that harbour type II but not type I NKT cells, and CD1d^-/- MHCII^-/- mice, lacking all NKT cells. We identified significantly larger populations of CD4⁺ and CD4^- CD8^- (double negative, DN) TCR?⁺ cells expressing NKG2D or NKG2A/C/E in J?18^-/- MHCII^-/- mice compared with CD1d^-/- MHCII^-/- mice, suggesting that 30%-50% of these cells were type II NKT cells. They expressed CD122, NK1.1, CXCR3 and intermediate/low levels of CD45RB. Further, the CD4⁺ subset was CD69⁺ , while the DN cells were CD49b⁺ and CD62L⁺ . Both subsets expressed the NKT cell-associated promyelocytic leukaemia zinc finger (PLZF) transcription factor and Tbet, while fewer cells expressed ROR?t. NKG2D⁺ CD4⁺ and DN populations were producers of IFN-?, but rarely IL-4 and IL-17. Taken together, we identify a novel subset of primary CD4⁺ and DN type II NKT cells that expresses NKG2 receptors have typical NKT cell phenotypes and a TH1-like cytokine production.

SUBMITTER: Singh AK 

PROVIDER: S-EPMC6851763 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature