CD1d is expressed on B‐chronic lymphocytic leukemia cells and mediates α‐galactosylceramide presentation to natural killer T lymphocytes

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Abstract
Generation of immune responses against B cell chronic lymphocytic leukemia (B‐CLL) has been the aim of several studies that have demonstrated a poor antigen presenting ability of B‐CLL cells and an inconsistent emergence of T cells capable of killing efficiently the leukemic cells. CD1d is a restriction element structurally related to the major histocompatibility complex (MHC) and capable of presenting lipid antigens to CD1d‐restricted T cells (also defined as natural killer‐T [NKT] cells). The synthetic lipid α‐galactosylceramide (α‐GalCer) has been characterized as a potent stimulator of CD1d‐restricted T cells. We have investigated the expression of CD1d on B‐CLL cells. CD1d was detected by flow cytometric analyses on leukemic cells of all B‐CLL cases studied (n = 38) and was expressed at higher density on cells carrying unmutated immunoglobulin variable region (IgV) genes. In addition, CD1d on B‐CLL cells mediated the presentation of α‐GalCer to CD1d‐restricted T cells, which in turn induced B‐CLL cell death. At variance with another study (Metelitsa et al., Leukemia 2003;17:1068–77), no correlation between expression levels of CD1d and susceptibility to NKT cell lysis was observed. Proliferation and production of interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) by CD1d‐restricted T cells, in the presence of B‐CLL cells loaded with α‐GalCer, were also observed. Our study demonstrates that B‐CLL cells express a monomorphic restriction element that is functionally capable of antigen presentation and can be useful to design novel B‐CLL immunotherapies.

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