Submitted April 7, 2008
Accepted May 23, 2008
Inflammation associated lysophospholipids as ligands for CD1d restricted T cells in human cancer
David H Chang, Haiteng Deng, Phillip Matthews, Joseph Krasovsky, Govind Ragupathi, Radek Spisek, Amitabha Mazumder, David H Vesole, Sundar Jagannath, and Madhav V Dhodapkar*
Laboratoy of Tumor Immunology and Immunotherapy, Rockefeller University, New York, NY, United States
Proteomics Resource Center, Rockefeller University, New York, NY, United States
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
Myeloma, St. Vincent's Cancer Center, New York, NY, United States
Section of Hematology, Yale University, New Haven, CT, United States
* Corresponding author; email: madhav.dhodapkar{at}yale.edu.
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 TCR
+ T cells but predominantly V24-V11-. Cytokine secretion by LPC specific T cells is skewed towards IL13 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.
