The contrasting roles of NKT cells in tumor immunity.
NKT cells are true T cells that serve as a bridge between the innate and adaptive immune system, acting as first responders. They recognize lipid antigens rather than peptides, and respond to these when presented by a non-classical class I MHC molecule, CD1d. NKT cells can play a pathogenic role in asthma or a protective role against several autoimmune diseases, in part based on their cytokine profile. In cancer, they can play opposite roles, contributing to anti-tumor immunity or suppressing it. The protective NKT cells were found to be primarily type I NKT cells defined by use of a semi-invariant T cell receptor involving Valpha14Jalpha18 in mice and Valpha24Jalpha18 in humans and responding to alpha-galactosylceramide, and the most protective were among the minority that are CD4-. The suppressive NKT cells were found to be CD4+ and to be primarily type II NKT cells, that have diverse T-cell receptors and respond to other lipids. Further, the type I and type II NKT cells were found to counter-regulate each other, forming a new immunoregulatory axis. This axis may have broad implications beyond cancer, as NKT cells play a role in steering other adaptive immune responses. The balance along this axis could affect immunity to tumors and infectious diseases and responses to vaccines.
Berzofsky
Jay A
JA
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA. berzofsk@helix.nih.gov
Terabe
Masaki
M
D000818:Animals; D006801:Humans; D055611:Natural Killer T-Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*
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