Nonconventional CD8+ T Cell Responses to <i>Listeria</i> Infection in Mice Lacking MHC Class Ia and H2-M3

Cho, Hoonsik; Choi, Hak Jong; Xu, Hui; Felio, Kyrie; Wang, Chyung Ru

doi:10.4049/jimmunol.1002639

Cited by 15 publications

(15 citation statements)

References 65 publications

(82 reference statements)

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“…Ϫ/Ϫ showed that non-H2-M3 MHC class Ib-restricted CD8 ϩ T cells express activated surface markers, exhibit cytotoxicity, and produce cytokines, including IFN-␥ and IL-17A, in response to L. monocytogenes infection (11). Although this response was not blocked by anti-MR1 MAb, based on our findings this could be due to non-MR1-dependent activation of MAIT cells.…”

Section: M3mentioning

confidence: 53%

“…Although this response was not blocked by anti-MR1 MAb, based on our findings this could be due to non-MR1-dependent activation of MAIT cells. Moreover, it is possible that the role of the MAIT cells in the CD4/CD8 DN T-cell population is overlooked in the studies focusing on CD8 ϩ T cells in Kb Ϫ/Ϫ Db Ϫ/Ϫ or Kb Ϫ/Ϫ Db Ϫ/Ϫ M3 Ϫ/Ϫ mice (11,76). In fact, a rare population of CD4 Ϫ CD8 Ϫ NK1.1 Ϫ ␣␤ T cells in WT mice was shown to inhibit the intracellular growth of M. tuberculosis and Francisella tularensis (LVS) (18,19), and these CD4/CD8 DN T cells secreted high levels of IFN-␥ and IL-17A in response to F. tularensis LVS infection (19).…”

Section: M3mentioning

confidence: 99%

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Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

et al. 2012

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ABSTRACTMucosa-associated invariant T (MAIT) cells are a unique population of αβ T cells in mammals that reside preferentially in mucosal tissues and express an invariant Vα paired with limited Vβ T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Usingin vitroassays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens. However, whether MAIT cells play an important, and perhaps unique, role in controlling microbial infection has remained unclear. To probe MAIT cell function, we show here that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth ofMycobacterium bovisBCG in macrophages (MΦ) in coculture assays, and this inhibitory activity was dependent upon MAIT cell selection by MR1, secretion of gamma interferon (IFN-γ), and an innate interleukin 12 (IL-12) signal from infected MΦ. Surprisingly, however, the cognate recognition of MR1 by MAIT cells on the infected MΦ was found to play only a minor role in MAIT cell effector function. We also report that MAIT cell-deficient mice had higher bacterial loads at early times after infection compared to wild-type (WT) mice, demonstrating that MAIT cells play a unique role among innate lymphocytes in protective immunity against bacterial infection.

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Section: M3mentioning

confidence: 53%

Section: M3mentioning

confidence: 99%

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

et al. 2012

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“…Using T-cell receptor (TCR) transgenic (Tg) mice, we have shown that M3 is necessary and sufficient for the selection of M3-restricted T cells with no contribution from MHC Ia or other MHC Ib molecules (14,15). Additionally, using a mouse model deficient in both MHC Ia and M3 molecules, we have shown that non-M3 MHC Ib-restricted CD8 + T cells are very similar to M3-restricted CD8 + T cells in terms of surface phenotype and expansion kinetics following LM infection (16). Based on this result, M3-restricted CD8 + T cells represent a reasonable model for the study of MHC Ib-restricted CD8 + T cells in general.…”

Section: Cd8 T Cells | H2-m3 | Innate Lymphocytes | T-cell Developmentmentioning

confidence: 85%

“…BMDCs were prepared as described previously (16). DCs were pulsed with 1 μM LemA peptide (fMIGWII) for 6 h and injected i.v.…”

Section: Methodsmentioning

confidence: 99%

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells

Cho

Bediako

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Several studies have demonstrated an apparent link between positive selection on hematopoietic cells (HCs) and an “innate” T-cell phenotype. Whereas conventional CD8 + T cells are primarily selected on thymic epithelial cells (TECs) and certain innate T cells are exclusively selected on HCs, MHC class Ib-restricted CD8 + T cells appear to be selected on both TECs and HCs. However, whether TEC- and HC-selected T cells represent distinct lineages or whether the same T-cell precursors have the capacity to be selected on either cell type is unknown. Using an M3-restricted T-cell receptor transgenic mouse model, we demonstrate that not only are MHC class Ib-restricted CD8 + T cells capable of being selected on either cell type but that selecting cell type directly affects the phenotype of the resulting CD8 + T cells. M3-restricted CD8 + T cells selected on HCs acquire a more activated phenotype and possess more potent effector functions than those selected on TECs. Additionally, these two developmental pathways are active in the generation of the natural pool of M3-restricted CD8 + T cells. Our results suggest that these two distinct populations may allow MHC class Ib-restricted CD8 + T cells to occupy different immunological niches playing unique roles in immune responses to infection.

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“…Impaired early bacterial clearance in H2-M3-deficient mice demonstrates a non-redundant role for H2-M3 in LM infection (29). The higher bacterial burden in K b−/− D b−/− M3 −/− mice compared to K b−/− D b−/− mice at day 7 post LM infection suggests that H2-M3 has protective function against LM infection (30). H2-M3-restricted T cell responses can also be demonstrated in Chlamydia pneumoniae , Mycobacterium tuberculosis , and Salmonella enterica infections (31–34).…”

Section: Introductionmentioning

confidence: 99%

An MHC Class Ib-Restricted CD8+ T Cell Response to Lymphocytic Choriomeningitis Virus

Chen

Jay

Fairbanks

et al. 2011

The Journal of Immunology

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Conventional MHC class Ia-restricted CD8+ T cells play a dominant role in the host response to virus infections but recent studies indicate that T cells with specificity for nonclassical MHC class Ib molecules may also participate in host defense. To investigate the potential role of class Ib molecules in anti-viral immune responses, Kb−/−Db−/−CIITA−/− mice lacking expression of MHC class Ia and class II molecules were infected with LCMV. These animals have a large class Ib-selected CD8+ T cell population and they were observed to mediate partial (but incomplete) virus clearance during acute LCMV infection as compared to Kb−/−Db−/−®2M−/− mice that lack expression of both MHC class Ia and class Ib molecules. Infection was associated with expansion of splenic CD8+ T cells and induction of granzyme B and IFN© effector molecules in CD8+ T cells. Partial virus clearance was dependent on CD8〈®+ cells. In vitro T cell re-stimulation assays demonstrated induction of a population of ®2M-dependent, MHC class Ib-restricted CD8+ T cells with specificity for viral antigen(s) and a yet to be defined nonclassical MHC molecule(s). MHC class Ib-restricted CD8+ T cell responses were also observed after infection of Kb−/−Db−/− mice, despite the low number of CD8+ T cells in these animals. Long term infection studies demonstrated chronic infection and gradual depletion of CD8+ T cells in Kb−/−Db−/−CIITA−/− mice, demonstrating that class Ia molecules are required for viral clearance. These findings demonstrate that class Ib-restricted CD8+ T cells have the potential to participate in the host immune response to LCMV.

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Nonconventional CD8+ T Cell Responses to Listeria Infection in Mice Lacking MHC Class Ia and H2-M3

Cited by 15 publications

References 65 publications

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells

An MHC Class Ib-Restricted CD8+ T Cell Response to Lymphocytic Choriomeningitis Virus

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Nonconventional CD8+ T Cell Responses to Listeria Infection in Mice Lacking MHC Class Ia and H2-M3

Cited by 15 publications

References 65 publications

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 + T cells

An MHC Class Ib-Restricted CD8+ T Cell Response to Lymphocytic Choriomeningitis Virus

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Product

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Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 ⁺ T cells