Comparative Contribution of CD1 on the Development of CD4+ and CD8+ T Cell Compartments

Wang, Bin; Chun, Taehoon; Wang, Chyung Ru

doi:10.4049/jimmunol.164.2.739

Cited by 10 publications

(9 citation statements)

References 59 publications

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“…In fact, in agreement with the findings reported here, it has been reported that CD4 ϩ T-cell lines recognizing lipid antigens presented by CD1 can be isolated both from human PBMC and from mice (26,35). Although proliferation assays may be biased because they preferentially detect strongly proliferating cells (i.e., CD4 ϩ cells), the results suggest that CD4 ϩ T cells could represent the major subset of T cells responsive to mycobacterial lipid antigens in humans.…”

Section: Cd8supporting

confidence: 80%

T-Cell Responses to CD1-Presented Lipid Antigens in Humans with Mycobacterium tuberculosis Infection

et al. 2003

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CD1-restricted presentation of lipid or glycolipid antigens derived fromMycobacterium tuberculosis is a human pathogen of enormous importance to global public health. According to the most recent data published by the World Health Organization, approximately 2.2 million deaths per year are attributable to M. tuberculosis, an additional 8 million people develop symptoms of tuberculosis (TB) every year, and every third human being on earth is infected with the bacterium (36). In spite of this devastating impact on human populations, it is also clear that the human immune system is capable of providing effective protection against disease due to M. tuberculosis infection, since the majority of immunocompetent people infected by this bacterium do not develop signs of serious illness. A major goal for future efforts to control tuberculosis is thus to understand how the immune system successfully recognizes and suppresses the growth of M. tuberculosis. Understanding the underlying mechanisms of the natural adaptive immune response to M. tuberculosis may allow development of novel vaccination strategies to control disease caused by this pathogen.A substantial body of clinical and experimental data indicate that antigen-specific T cells play a major role in maintaining solid and long-lived immunity to M. tuberculosis (reviewed in reference 4). It also has been shown for animal models and for humans that both CD4 ϩ and CD8 ϩ T cells are involved in the adaptive immune response to the pathogen (4, 24, 25). Thus, both classical pathways of antigen presentation, which depend on the peptide binding and presenting functions of the major histocompatibility complex (MHC) class I and class II molecules, have been shown to be involved in the protective immune response to M. tuberculosis. However, it has also become clear in recent years that CD1 molecules, a family of antigenpresenting molecules that bind lipids and present these to T cells, are also involved in the generation of cell-mediated immune responses to mycobacterial pathogens (6,21,33). The precise role and relative importance of this novel pathway for antigen recognition in generating protective immunity to M. tuberculosis remains poorly understood.Studies of the human CD1 system have identified this as a family of antigen-presenting molecules related in structure and evolution to MHC class I and class II molecules (21). CD1 is conserved in most or all mammals, although the size and number of CD1 genes and the variety of different CD1 isoforms vary widely among species. In humans, the CD1 family consists of five isoforms (CD1a, -b, -c, -d, and -e) encoded by a cluster of minimally polymorphic genes that map outside of the MHC. The current system of classification divides the human CD1 proteins into at least two distinct groups (group 1 and group 2) based on differences in structure, expression, and function. Group 1 CD1 proteins, which include CD1a, -b, and -c, are expressed predominantly on professional antigen-presenting

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Section: Cd8supporting

confidence: 80%

T-Cell Responses to CD1-Presented Lipid Antigens in Humans with Mycobacterium tuberculosis Infection

et al. 2003

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“…Interestingly, the remaining CD1d-restricted CD4 ϩ NK1.1 Ϫ cells also display limited TCR diversity (44). However, in CD1 o TAP o mice, as compared with TAP o mice, no significant differences in the CD8 ϩ T cell compartment could be detected (43,44). Thus, despite the fact that CD8 seems to be a coreceptor for CD1d (45,46), CD1d fails to contribute significantly to the development of CD8 ϩ T cells.…”

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

confidence: 82%

“…No detectable changes were observed in either CD4 ϩ or CD8 ϩ populations in CD1 o mice (40 -42), suggesting that the presence of MHC class Ia and class II molecules in these mice may obscure any role of CD1d in selection of conventional T cell populations. Indeed, the number of CD4 ϩ T cells in CD1 o II o mice was reduced significantly compared with the corresponding population in II o mice (43,44). Although the observed differences between CD1 o II o and II o mice were largely attributed to the loss of CD1d-restricted CD4 ϩ NKT cells, a small population of CD4 ϩ NK1.1 Ϫ T cells was also reduced in CD1 o II o mice.…”

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

confidence: 87%

“…We and others have previously shown that CD1d does not contribute significantly to the development of CD8 ϩ T cells (43,44). One possible explanation for the limited impact of CD1d on the generation of the CD8 ϩ T cell repertoire is relatively low surface expression and distinct tissue distribution as compared with MHC class Ia molecules.…”

Section: Cd1d Expression In K B -Cd1dtg Mice Mimics H-2k B Expressionmentioning

confidence: 99%

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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

The Journal of Immunology

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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.

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“…3,4,10 As CD1d molecules are vital for NKT cell development, 5 mice lacking the CD1d1 gene (CD1KO mice) are deficient in all CD1d-restricted NKT cells. 11,12 Mice lacking the Ja18 gene (Ja18KO mice) are deficient in iNKT cells, but the TCR repertoire of these mice includes CD1d-restricted NKT cells that use diverse ab TCR and gd TCR genes [variant NKT (vNKT)] cells. 13 The vast majority of NKT cells (>90%) use Va14Ja18 TCRa chain rearrangement in mice 14 and Va24Ja18 in humans, 15 are present in a wide variety of mouse strains, absent in mice deficient in b2-microblobulin 16 and are present in mice deficient in the MHC class I peptide transporter, TAP1.…”

mentioning

confidence: 99%

Inhibition of antitumor immunity by invariant natural killer T cells in a T‐cell lymphoma model in vivo

Renukaradhya

Sriram

et al. 2006

Intl Journal of Cancer

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We have investigated the role of the host's CD1d-dependent innate antitumor immune response in a murine T-cell lymphoma model in vivo. We found that C57BL/6 wildtype (WT) mice inoculated with RMA/S cells transfected with murine CD1d1 died at the same rate as mice inoculated with vector-transfected cells. In contrast, natural killer T (NKT) cell-deficient CD1d or Ja18 knockout mice inoculated with CD1d-transfected RMA/S cells survived significantly longer than mice inoculated with vector-transfected RMA/S cells, implicating the involvement of invariant NKT (iNKT) cells in inhibiting antitumor activity in vivo. In contrast to the mutant mice, which produced more of the proinflammatory cytokines IFN-c and GM-CSF, WT mice produced significantly elevated amounts of IL-13. Antitumor activity in the knockout mice was not due to the development of CD1d-specific cytotoxic T lymphocytes or circulating antibodies. However, iNKT cell numbers were elevated in tumor-bearing mice. Thus, iNKT cells may be playing a negative role in the host's antitumor immune response against T-cell lymphomas in a CD1d-dependent manner. ' 2006 Wiley-Liss, Inc.Key words: T-cell lymphoma; RMA/S; invariant NKT cells; CD1d molecules; cytokines Despite apparent immunocompetence in the host, lymphomas can arise nonetheless, evading the body's attempts at tumor immunosurveillance. Following transformation, the host's innate immune response is essential in controlling the dissemination and growth of metastatic disease. Immunosurveillance against spontaneously occurring lymphomas is not well understood. Understanding the molecular mechanisms that regulate divergent arms of the immune response is a key to develop effective immunotherapies for many diseases, including cancer.1 Recent studies have suggested an immunosurveillance function for a unique subpopulation of T cells that play an important role in innate immunity called natural killer T (NKT) cells.2 NKT cells are defined as T cells expressing markers on the surface shared with NK cells, and that rapidly secrete both Th1 and Th2 cytokines upon T-cell receptor (TCR) ligation. 3,4 Rather than recognizing peptides presented by MHC class I or class II molecules, NKT cells recognize lipid antigens presented by the MHC class I-like CD1d molecule.5 NKT cells are key players in the regulation of antitumor immunity, particularly in experimental models of tumor immunotherapy, including IL-12 or a-galactosylceramide (a-GalCer) administration.6 In a mouse model in which tumors spontaneously regress after initial growth and then recur, the negative regulation of tumor immunosurveillance by IL-13, possibly produced by CD41 NKT cells, has been reported. 7,8 In a more recent study, the same group has shown that a reduction in pulmonary metastases in the CT26 nonregressor colon carcinoma model occurs following the elimination of CD4 1 NKT cells, further illustrating an inhibitory role for NKT cells in antitumor immunity. 9 To date, the role of invariant (Va14Ja18 1 ) NKT (iNKT) cells in the evasion of hematopoieti...

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Comparative Contribution of CD1 on the Development of CD4+ and CD8+ T Cell Compartments

Cited by 10 publications

References 59 publications

T-Cell Responses to CD1-Presented Lipid Antigens in Humans with Mycobacterium tuberculosis Infection

T-Cell Responses to CD1-Presented Lipid Antigens in Humans with Mycobacterium tuberculosis Infection

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

Inhibition of antitumor immunity by invariant natural killer T cells in a T‐cell lymphoma model in vivo

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