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CD1d is expressed on B‐chronic lymphocytic leukemia cells and mediates α‐galactosylceramide presentation to natural killer T lymphocytes
Author(s) -
Fais Franco,
Morabito Fortunato,
Stelitano Caterina,
Callea Vincenzo,
Zanardi Sabrina,
Scudeletti Marco,
Varese Paola,
Ciccone Ermanno,
Grossi Carlo Enrico
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11723
Subject(s) - cd1d , cd1 , natural killer t cell , biology , antigen presentation , chronic lymphocytic leukemia , antigen , antigen presenting cell , immune system , cd40 , cytotoxic t cell , major histocompatibility complex , immunology , t cell , leukemia , microbiology and biotechnology , in vitro , biochemistry
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.