Murine CD1d‐restricted gamma‐delta T cells respond to cardiolipin

Abstract

CD1d recognizes both microbial and self‐antigens, but the nature of the endogenous lipids bound by CD1d remains poorly elucidated. Cardiolipin (CL) is a major phospholipid component of bacteria that have been shown to trigger strong CD1d‐restricted responses. CL is also present in mammalian cells, but normally hidden from the immune system because of its location in the mitochondrial inner membrane. Based on growing evidence that CD1‐restricted T cells recognize phospholipids, we hypothesized that T cells in the normal immune repertoire respond to CL. Splenocytes, or liver‐derived lymphocytes, from C57BL/6 mice were incubated with bovine heart CL or control phospholipids. Proliferation occurred exclusively with CL, in a dose‐dependent manner, and was greatest in liver‐derived cells. CL‐dependent T cell stimulation was abrogated by monoclonal anti‐CD1 antibody, but was unaffected by antibody against MHC I or II. Furthermore, CL‐dependent T cell stimulation was undetectable in cells isolated from CD1d‐deficient mice. Using flow cytometry, CL‐responsive cells were shown to express gamma‐delta T cell receptor (TCR) and to produce interferon‐gamma. These findings demonstrate that a subset of CD1d‐restricted gamma‐delta T cells responsive to CL exists in the liver of healthy mice, and suggest that these cells could play a role in T cell responses to bacteria and, potentially, to self‐CL.Supported by CIHR (JR).