Liver CD4−CD8− NK1.1+ TCRαβ Intermediate Cells Increase During Experimental Malaria Infection and Are Able to Exhibit Inhibitory Activity Against the Parasite Liver Stage In Vitro

109

The onset of autoimmune diabetes is related to defective immune regulation. Recent studies have shown that NK T cells are deficient in number and function in both diabetic patients and nonobese diabetic (NOD) mice. NK T cells, which are CD1d restricted, express a TCR with an invariant Vα14-Jα281 chain and rapidly produce large amounts of cytokines. Vα14-Jα281 transgenic NOD mice have increased numbers of NK T cells and are protected against diabetes onset. In this study we analyzed where and how NK T cells interfere with the development of the anti-islet autoimmune response. NK T cells, which are usually rare in lymph nodes, are abundant in pancreatic lymph nodes and are also present in islets. IL-4 mRNA levels are increased and IFN-γ mRNA levels decreased in islets from diabetes-free Vα14-Jα281 transgenic NOD mice; the IgG1/IgG2c ratio of autoantibodies against glutamic acid decarboxylase is also increased in these mice. Treatment with IL-12 (a pro-Th1 cytokine) or anti-IL-4 Ab abolishes the diabetes protection in Vα14-Jα281 NOD mice. The protection from diabetes conferred by NK T cells is thus associated with a Th2 shift within islets directed against autoantigen such as glutamic acid decarboxylase. Our findings also demonstrate the key role of IL-4.

Section: Nk T Cell-induced Protection Against Diabetes In V␣14-mentioning

confidence: 99%

NK T Cell-Induced Protection Against Diabetes in Vα14-Jα281 Transgenic Nonobese Diabetic Mice Is Associated with a Th2 Shift Circumscribed Regionally to the Islets and Functionally to Islet Autoantigen

Laloux

Beaudoin

Jeske

et al. 2001

109

“…This rapid response implicates NKT cells in a role branching innate and adaptive immunity. Indeed, NKT cells have been implicated in protective roles in bacterial and parasitic infection (22)(23)(24), tumor responses (25,26), and prevention against various autoimmune diseases such as type I diabetes (27)(28)(29)(30) and multiple sclerosis (31)(32)(33).…”

Section: Expression Of Cd1d Under the Control Of A Mhc Class Iamentioning

confidence: 99%

Expression of CD1d Under the Control of a MHC Class Ia Promoter Skews the Development of NKT Cells, But Not CD8+ T Cells

Chun

Colmone

et al. 2003

Although CD1d and MHC class Ia share similar overall structure, they have distinct levels and patterns of surface expression. While the expression of CD1d1 is known to be essential for the development of NKT cells, the contribution of CD1d1 to the development of CD8+ T cells appears to be inconsequential. To investigate whether CD1d tissue distribution and expression levels confer differential capacity in selecting these two T cell subsets, we analyzed CD8 and NKT cell compartments in Kb-CD1d-transgenic mice that lack endogenous MHC class Ia and CD1d, respectively. We found that MHC class Ia-like expression pattern and tissue distribution are not sufficient for CD1d to rescue the development of CD8+ T cells, suggesting that unique structural features of CD1d preclude its active participation in selection of CD8+ T cells. Conversely, cell type-specific CD1d surface density is important for the selection of NKT cells, as the NKT cell compartment was only partially rescued by the Kb-CD1d transgene. We have previously demonstrated that increased CD1d expression on dendritic cells enhanced negative selection of NKT cells. In this study, we show that cell type-specific expression levels of CD1d establish a narrow window between positive and negative selection, suggesting that the distinct CD1d expression pattern may be selected evolutionarily to ensure optimal output of NKT cells.

“…Recent studies indicate that a novel subset of T cells, termed NKT cells, which share some surface molecules with NK cells, are important in the early stages of the immune response to a number of infectious agents (5)(6)(7)(8)(9)(10)(11)(12). A subset of these cells appears to recognize Ags presented by CD1 (13).…”

mentioning

confidence: 99%

“…CD1 and/or NKT cells have been implicated in immunity to a number of pathogens. For example, protection of mice against the malaria parasite Plasmodium yoelii has been shown to involve NKT cells (10,11). IFN-␥ production by NKT cells appears to be important in the protective immune response to Toxoplasma gondii (12), and NKT cells are important for clearance of hepatitis B virus (HBV) from hepatocytes in HBV Agexpressing transgenic mice treated with ␣-GalCer (21).…”

mentioning

confidence: 99%

Impaired Clearance of Herpes Simplex Virus Type 1 From Mice Lacking CD1d or NKT Cells Expressing the Semivariant Vα14-Jα281 TCR

Grubor‐Bauk

Simmons

Mayrhofer

et al. 2003

184

141

Ag-presenting molecule CD1 and CD1-restricted NKT cells are known to contribute to defense against a range of infectious pathogens, including some viruses. CD1-restricted NKT cells, a distinct subpopulation of T cells, have striking and rapid effector functions that contribute to host defense, including rapid production of IFN-γ and IL-4, and activation of NK cells. Consideration of the important contributions of innate and adaptive immunity to clearance of HSV prompted us to investigate the role of CD1 and of NKT cells expressing the Vα14-Jα281 TCR in the pathogenesis of HSV infection. To address this issue, we compared infection in wild-type mice with that in CD1 gene knockout (GKO) and Jα281 GKO mice. In this study, we report impaired clearance of virus and viral Ags, and more florid acute infection in mice lacking CD1 (and by inference, CD1-restricted T cells), in comparison with parental C57BL6 mice. In Jα281 GKO mice there was also impairment of virus clearance, resembling that seen in CD1 GKO mice. These results imply roles for the Vα14-Jα281 subset of NKT cells and for CD1d in control of HSV infection.