Immunologic Research

, Volume 30, Issue 2, pp 139-153

First online:

Regulation of immune responses by CD1d-restricted natural killer T cells

  • Luc Van KaerAffiliated withDepartment of Microbiology and Immunology, Vanderbilt University School of Medicine Medical Center North Email author 

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Natural killer T (NKT) cells are a unique subset of T lymphocytes that share receptor structures and properties with conventional T lymphocytes and natural killer (NK) cells. NKT cells are specific for glycolipid antigens such as the marine sponge-derived agent α-galactosylceramide (α-GalCer) presented by the major histocompatibility complex (MHC) class I-like molcule CD1d. My laboratory has evaluated the function of NKT cells by generating and analyzing CD1d-deficient mice. These studies showed that CD1d expression is required for NKT cell development, but not absolutely necessary for the generation of polarized T helper (Th) cell responses. Further, we have studied the in vivo response of NKT cells toα-GalCer stimulation and the capacity of α-GalCer to modulate innate and adaptive immune responses. Our results revealed that, quickly following administration of α-GalCer, NKT cells expand and produce cytokines, trans-activate a variety of innate and adaptive immune cells, and promote Th2 responses that are capable of suppressing Th1-dominant autoimmunity. Our findings indicate that NKT cells play a regulatory role in the immune response and that specific activation of these cells may be exploited for therapeutic purposes.

Key Words

α-Galactosylceramide Antigen presentation Autoimmunity Experimental autoimmune encephalomyelitis CD1d Glycolipids Immunomodulation Immunotherapy Natural killer T cells Type 1 diabetes