Inflammation-associated lysophospholipids as ligands for CD1d-restricted T cells in human cancer.
CD1d-restricted T cells have been implicated in the pathogenesis of several chronic inflammatory states. However, the nature of the specific ligands recognized by these cells in vivo in patients with inflammatory or malignant diseases remains unknown. We took a biochemical approach to directly isolate and characterize the nature of CD1d-binding ligands from the plasma of myeloma patients. Characterization of these ligands revealed several lysophosphatidylcholine (LPC) species. Human LPC-CD1d dimer binding cells are T-cell receptoralphabeta(+) T cells but predominantly Valpha24(-)Vbeta11(-). Cytokine secretion by LPC-specific T cells is skewed toward IL-13 secretion, and the frequencies of these cells are increased in myeloma patients relative to healthy donors. These data identify a distinct population of human CD1d-restricted T cells specific for inflammation-associated lysolipids and suggest a novel mechanism for inflammation mediated immune regulation in human cancer.
Laboratory of Tumor Immunology and Immunotherapy, Rockefeller University, New York, NY, USA.
David H
DH
Chang
Haiteng
H
Deng
Phillip
P
Matthews
Joseph
J
Krasovsky
Govind
G
Ragupathi
Radek
R
Spisek
Amitabha
A
Mazumder
David H
DH
Vesole
Sundar
S
Jagannath
Madhav V
MV
Dhodapkar
D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018793:Interleukin-13 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008244:Lysophosphatidylcholines / Q000032:analysis; D008246:Lysophospholipids / Q000276:immunology* / Q000378:metabolism; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D018949:Antigens, CD1; D018793:Interleukin-13; D008024:Ligands; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D016693:Receptors, Antigen, T-Cell, alpha-beta