Type II NKT Cells in Inflammation, Autoimmunity, Microbial Immunity, and Cancer

Abstract

Natural killer T cells (NKT) recognize self and microbial lipid antigens presented by non-polymorphic CD1d molecules. Two major NKT cell subsets, type I and II, express different types of antigen receptors (TCR) with distinct mode of CD1d/lipid recognition. Though type II NKT cells are less frequent in mice and difficult to study, they are predominant in human. One of the major subsets of type II NKT cells reactive to the self-glycolipid sulfatide is the best characterized and has been shown to induce a dominant immune regulatory mechanism that controls inflammation in autoimmunity and in anti-cancer immunity. Recently, type II NKT cells reactive to other self-glycolipids and phospholipids have been identified suggesting both promiscuous and specific TCR recognition in microbial immunity as well. Since the CD1d pathway is highly conserved, a detailed understanding of the biology and function of type II NKT cells as well as their interplay with type I NKT cells or other innate and adaptive T cells will have major implications for potential novel interventions in inflammatory and autoimmune diseases, microbial immunity, and cancer.

Reconstruction of NK Cells During Complex Cancer Treatment

“…Support of anticancer immunity is connected with NKT type I, whereas type II is involved in the suppression of anticancer defense [20] . NK cells type I induce lysis of cancer cells both directly (via perforin/granzyme mechanisms) and indirectly (via induction of secretion of Th1 cytokines and NK cell activation).…”

“…A direct proof of the role of leptin in breast cancer induction was demonstrated in a mouse study where leptin-deficient mice (ob/oba or ob/ob) did not suffer from experimental breast tumors [5] . In NK cells leptin is involved in cell development, differentiation, proliferation, activation and toxicity [7,20] . These actions are mediated partly via activation of signal transducers and activators of transcription 295 ± 14 cells/mL (P ≤ 0.02), whereas in the placebo group there was nonsignificant decrease from 239 ± 17 to 200 ± 15 cells/mL ( Figure 2).…”

Mechanisms and Consequences of Antigen Presentation by CD1

“…Importantly, dNKT cells are more prevalent in humans than in mice. Like iNKT cells, dNKT cells express PLZF [92], exhibit innate-like functions and can influence a wide variety of immune responses [47, 93, 94]. An interesting phenomenon is that dNKT cells often oppose the functions of iNKT cells [95].…”

The Crosstalk between Myeloid Derived Suppressor Cells and Immune Cells: To Establish Immune Tolerance in Transplantation

“…NKT cells can be divided into two subtypes: type I NKT cells, also known as inducible NKT cells, participate in antitumor immunity, and on the contrary, type II NKT cells facilitate tumor progression [28, 29]. The investigations on the relationship between MDSC and NKT cells are limited.…”