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

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. © 2004 Wiley-Liss, Inc.