Phospholipid-reactive T cells negatively regulate the function and expansion of glycolipid-reactive T cells (P4012)

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Abstract Glycolipid antigens such as αGalCer and phospholipid (PL) antigens such as phosphatidyl choline bind CD1d and activate T cells. Extensive work on αGalCer-reactive T cells has identified their pathogenic or protective roles in inflammation, infection and cancer. Little is known about the biology and functions of CD1d-restricted PL-reactive T (PL-T) cells. Here, we identified T cells that recognize a battery of PL antigens loaded onto mouse CD1d in various lymphoid organs. While CD1d/PL-T cells were fewer than CD1d/αGalCer-reactive T cells in the liver and spleen, PL-T cells were relatively more abundant than glycolipid-reactive T cells in organs such as mouse decidua. The CD1d/PL-T cells secreted IFN-γ upon in vivo priming with PL antigens in an antigen-specific manner. The PL-T cells did not stain with CD1d/αGalCer tetramers and did not respond to glycolipid antigen αGalCer. Intriguingly, activation of CD1d/PL-T cells markedly reduced the proliferation of αGalCer-reactive T cells in vitro, ex vivo, and in vivo. Thus, PL-T cells are a subset of CD1d-restricted T cells that are phenotypically and functionally distinct from glycolipid-reactive T cells. PL-T cells also negatively regulate the function of glycolipid-reactive T cells. Ongoing studies will investigate whether PL-T cells will modulate the pathogenic and protective roles of glycolipid-reactive T cells in various immune-mediated conditions.