A NK1.1+ Thymocyte-Derived TCR β-Chain Transgene Promotes Positive Selection of Thymic NK1.1+ αβ T Cells

Viret, Christophe; Lantz, Olivier; He, Xin; Bendelac, Albert; Janeway, Charles A.

doi:10.4049/jimmunol.165.6.3004

Cited by 9 publications

(6 citation statements)

References 60 publications

(43 reference statements)

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“…We therefore used an alternative strategy based on the transgenic expression of a Vβ6 + TCRβ chain from one of the iVα19 T-T hybridoma. As shown previously for mainstream T cells [26] and NKT cells [27], the frequency of the iVα19-Jα33 TCRα chain was increased in these mice in a MR1-dependent manner (see Figure S3D and Text S1). …”

Section: Resultssupporting

confidence: 81%

Stepwise Development of MAIT Cells in Mouse and Human

et al. 2009

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Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)α (iTCRα) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanVα7.2 antibody and MAIT cell-specific iTCRα and TCRβ transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRα and TCRβ transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%–4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and γδ T cells.

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Section: Resultssupporting

confidence: 81%

Stepwise Development of MAIT Cells in Mouse and Human

et al. 2009

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“…Another possibility is that the thymic architecture in TCR-transgenic animals is not formed properly and perhaps SLAM signaling is aborted. Finally, those TCRtransgenic animals that do have iNKT cells express a Vb gene that has been shown to associate with the invariant Va14 TCR chain in iNKT cells [1,2], and transgenic expression of such a compatible Vb chain has been shown to promote iNKT cell development [51]. P14 and DO11.10 mice express Vb8 (Vb8.1 and Vb8.2, respectively), while OT-I and OT-II mice express Vb5.…”

Section: Discussionmentioning

confidence: 99%

Immediate antigen‐specific effector functions byTCR‐transgenic CD8⁺ NKT cells

Wingender¹,

Berg²,

Jüngerkes³

et al. 2006

Eur J Immunol

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Only recently have natural antigens for CD1d-dependent, invariant Va14 + natural killer T (iNKT) cells been identified. Similar data for CD1d-independent and CD8 + NKT cell populations are still missing. Here, we show that the MHC class I-restricted CD8 + TCRtransgenic mouse lines OT-I, P14 and H-Y contain a significant proportion of transgenic CD8 + NK1.1 + T cells. In liver, most of NK1.1 + T cells express CD8aa homodimers. Transgenic NKT cells did not bind invariant Va14-to-Ja18 TCR rearrangement (Va14i)-specific CD1d/a-galactosylceramide tetramers and the frequency of iNKT cells was severely reduced. The activated cell surface phenotype and the distribution of transgenic NKT cells in vivo were similar to that reported for iNKT cells. The OT-I and P14 CD8 + NKT cells recognized their cognate antigen in the context of H2-K b and produced cytokines shortly after TCR stimulation. Importantly, transgenic NKT cells exerted immediate antigen-specific cytotoxicity in vitro and in vivo. Our results demonstrate the presence of transgenic CD8 + NKT cells in MHC class I-restricted TCR-transgenic animals, which are endowed with rapid antigen-specific effector functions. These data imply that experiments studying naive T cell function in TCR-transgenic animals should be interpreted with caution, and that such animals could be utilized for studying CD8 + NKT cell function in an antigen-specific manner.

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“…The competing model would predict that akin to mainstream T cells, Tcr gene segments rearrange randomly and the productive ones are subjected to positive and negative selection by CD1d1 and beget the NK T lineage -the stochastic model. Nucleotide sequence analyses of the V and J junctions within rearranged Va14Ja15 genes revealed that the canonical TCRa sequence of the CD1d1-reactive NK T cells is put together by random events that also include N nucleotide additions [133,172,173]. Moreover, the second allele also showed evidence of random rearrangement within the Tcr locus [133,172,173].…”

Section: Nk T Cell Ontogenymentioning

confidence: 99%

“…Nucleotide sequence analyses of the V and J junctions within rearranged Va14Ja15 genes revealed that the canonical TCRa sequence of the CD1d1-reactive NK T cells is put together by random events that also include N nucleotide additions [133,172,173]. Moreover, the second allele also showed evidence of random rearrangement within the Tcr locus [133,172,173]. More recently, genomic DNA sequence analysis of NK T cell-derived Vb8.2 transgenic thymocytes prior to selection (TCR low thymocytes) revealed random rearrangement of Va14 with Ja15 segments resulting in a high frequency of noncanonical Va14+ TCR a chain [173].…”

Section: Nk T Cell Ontogenymentioning

confidence: 99%

“…More recently, genomic DNA sequence analysis of NK T cell-derived Vb8.2 transgenic thymocytes prior to selection (TCR low thymocytes) revealed random rearrangement of Va14 with Ja15 segments resulting in a high frequency of noncanonical Va14+ TCR a chain [173]. The frequency of the canonical Va14Ja15+ TCR a chain containing the canonical sequence increased within the Vb8.2 transgenic thymocytes following positive selection (TCR int thymocytes) by CD1d1 [173]. Together, these data support the stochastic model for thymocyte commitment to the NK T lymphocyte lineage.…”

Section: Nk T Cell Ontogenymentioning

confidence: 99%

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CD1d and natural T cells: how their properties jump-start the immune system

Joyce¹

2001

CMLS, Cell. Mol. Life Sci.

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Cellular and humoral immune mechanisms recruited to defend the host from infectious agents depend upon the early immune events triggered by antigen. The cytokine milieu within which the immune response matures is the most important of many factors that govern the nature of the immune response. Natural T cells, whose function is controlled by CD1d molecules, are an early source of cytokines that can bestow type 1 or type 2 differentiative potential upon helper T lymphocytes. This review attempts to illuminate the glycolipid antigen presentation properties of CD1d, how CD1d controls the function of natural T cells and how CD1d and natural T cells interact to jump start the immune system. CD1d is postulated to function as a sensor, sensing alterations in cellular lipid content by virtue of its affinity for such ligands. The presentation of a neo-self glycolipid, presumably by infectious assault of antigen-presenting cells, activates natural T cells, which promptly release pro-inflammatory and anti-inflammatory cytokines and jump-start the immune system.

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A NK1.1+ Thymocyte-Derived TCR β-Chain Transgene Promotes Positive Selection of Thymic NK1.1+ αβ T Cells

Cited by 9 publications

References 60 publications

Stepwise Development of MAIT Cells in Mouse and Human

Stepwise Development of MAIT Cells in Mouse and Human

Immediate antigen‐specific effector functions byTCR‐transgenic CD8⁺ NKT cells

CD1d and natural T cells: how their properties jump-start the immune system

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A NK1.1+ Thymocyte-Derived TCR β-Chain Transgene Promotes Positive Selection of Thymic NK1.1+ αβ T Cells

Cited by 9 publications

References 60 publications

Stepwise Development of MAIT Cells in Mouse and Human

Stepwise Development of MAIT Cells in Mouse and Human

Immediate antigen‐specific effector functions byTCR‐transgenic CD8+ NKT cells

CD1d and natural T cells: how their properties jump-start the immune system

Contact Info

Product

Resources

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Immediate antigen‐specific effector functions byTCR‐transgenic CD8⁺ NKT cells