CD1d is expressed on B-chronic lymphocytic leukemia cells and mediates alpha-galactosylceramide presentation to natural killer T lymphocytes.
Int J Cancer
; 109(3): 402-11, 2004 Apr 10.
Article
en En
| MEDLINE
| ID: mdl-14961579
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 alpha-galactosylceramide (alpha-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 alpha-GalCer to CD1d-restricted T cells, which in turn induced B-CLL cell death. At variance with another study (Metelitsa et al., Leukemia 2003;171068-77), no correlation between expression levels of CD1d and susceptibility to NKT cell lysis was observed. Proliferation and production of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) by CD1d-restricted T cells, in the presence of B-CLL cells loaded with alpha-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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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Linfocitos T
/
Leucemia Linfocítica Crónica de Células B
/
Presentación de Antígeno
/
Antígenos CD1
/
Galactosilceramidas
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
Límite:
Humans
Idioma:
En
Revista:
Int J Cancer
Año:
2004
Tipo del documento:
Article
País de afiliación:
Italia