NKT-Cell Development

NKT-cell development is dependent on the protease cathepsin L. As NKT cells react to lipids, cathepsin L may process a lipid carrier protein that is required for loading lipids onto CDld. A strong candidate for the lipid carrier protein is prosaposin, a precursor that is cleaved into a series of lipid transfer proteins. As the structure of lipids capable of binding CDld is not as diverse as peptides, it is perhaps not surprising that NKT cells exhibit a limited TCR repertoire. The CD Id-restricted NKT cells also differ from mainstream T cells in co-receptor expression. They are CD4+ or double negative, and never CD8. ... 

Pasquier B, Yin L, Fondaneche MC et al 2005 Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product. Exp Med 201 695—701... 

Matsuda JL, Zhang Q, Ndonye R, Richardson SK, Howell AR, Gapin L. T-bet concomitantly controls migration, survival and effector functions during the development of Va 14i NKT cells. Blood 2006 107 2795-2805. 

Moodycliffe, A. M. et al., Immune suppression and skin cancer development Regulation by NKT cells, Nature Immunol. 1, 521-525, 2000. 

Mieza MA, Itoh T, Cui JQ, Makino Y, Kawario T, Tsushida K, Koike T, Slrirai T, Yogita H, Matsuzawa A, Koseki H, Tariiguchi M (1996) Selecdve reducdon of V alpha 14-l-NKT cells associated widi disease development in autoimmune-prone mice. J Immunol 156 4035 040. 

One lineage choice that occurs rather late in T-cell ontogeny is the development of NKT cells. NKT cells express markers of both NK cells and T lymphocytes. These include Ly49 family receptors NKl.l and TCR in mice. Mature NKT cells are CD44 CD69, a phenotype consistent with an activated cell. A hallmark of NKT cells is copious IL-4 and IFN-y secretion promptly upon TCR activation. Because of this property, NKT cells most Likely possess regulatory fimctions. They suppress multiple autoimmune phenomena, and in some cases, inhibit tumor metastases. Unlike conventional a 3 T cells that are selected by classical MHC class I and II, the vast majority of NKT cells are selected by the non-polymoiphic class I-like molecule, CD Id. 

OCH (17, Fig. 19) is the pioneering Th2-type glycolipid. Its development was reported by Yamamura, Miyake, and coworkers in 2001 [37]. It causes NKT cells to produce IL-4 predominantly in mice in vivo therefore, it can be... 

Colonization with helminths prevent onset of diabetes in the NOD murine model of TID. NOD mice exposed to S. mansoni are protected from developing diabetes. Schistosome egg or antigen e q>osure induces immune regulatory ILIO and augments NKT cell activity that may help prevent insulinitis. Colonization with T. spiralis or H. polygyrus also inhibits diabetes in NODmice. ... 

VDUPl mice displayed immune system defects, including perturbed development and function of natural killer (NK) cells. There was a profound reduction in the numbers of NK cells and in NK activity in VDUP1 mice, which showed minimal changes in T and B cell development (Lee et al. 2005). The NK cell abnormality in the VDUP1 mice caused severe lymphoid hyperplasia in the small intestine and reduced tumor rejection (Lee et al. 2005). Moreover, the percentage of hepatic natural killer T (NKT) cells in VDUPl" " mice was decreased, and the percentage... 

Other immune cells that have been implicated in atherogenesis are natural killer (NK) T-cells (NKTs) and dendritic cells (DCs). NKTs have a key role in innate immunity and have been detected in human and murine atherosclerotic lesions. LDL receptor (LDLR)-deficient mice depleted of functional NKTs exhibit a reduction in lesion formation, indicating that recruitment of these cells into the vessel wall contributes to the development of atherosclerosis (Whitman et al, 2004). DCs have a crucial role in the initiation of immune responses and are key antigen-presenting cells. Although their role in atherosclerosis is still unclear, they have been identified in the intima of human lesions and at arterial branch points in animal models, where they localize with T-cells and macrophages (Lord and Bobryshev, 2002). 

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