Regulation of the induction and function of cytotoxic T lymphocytes by natural killer T cell

Abstract

Cytotoxic T lymphocytes (CTLs) play a crucial role in the infections and the antitumor immunity. Induction and activation of antigen-specific CTLs is an important strategy in immunotherapy for various diseases, and several researchers have focused on the modulation of CTL induction and function. Natural killer T (NKT) cells are an important focus area of researchers studying immunomodulatory responses to tumors and infectious diseases. CD1d-restricted NKT cells consist of type I NKT cells and type II NKT cells. alpha-galactosylceramide (alpha-GalCer)-activated type I NKT cells secrete both Th1 (e.g., IFN-gamma) and Th2 cytokines, affect the expression of costimulatory molecules in immune cells, and regulate the host immune system. Type II NKT cells, however, are stimulated by sulfatide, a self-glycolipid derived from myelin, and play an immunosuppressive role in animal model of autoimmune diseases. CTL generation, activation, and suppression are strongly affected by activated type I and type II NKT cells. Thus, the regulation of these NKT cells leads to the modification of CTL function. CTLs contribute to antimicrobial responses, antitumor immune and autoimmune responses. Understanding the role of NKT cells in the regulation of CTL generation, activation, and suppression enable the development of novel treatment strategies for these diseases.

Figure 1

Cellular and molecular mechanisms of CTLs responses mediated by type I and type II NKT cells. Activated type I NKT cells have two distinct effects that regulate CTL function. CTLs are activated by type I NKT cells via cytokines (IL-2, IL-12, IFN-γ, and TNF-α) and costimulatory molecules (CD40L and CD28). In contrast, increased expression of Th2 cytokines (IL-4) and other costimulatory molecules (CTLA-4 and PD-L) inhibits CTL production or activation. Activated type II NKT cells suppress CTL activity via cytokines (IL-4, IL-13, and TGF-β).