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Review
. 2018 May 15;200(10):3333-3339.
doi: 10.4049/jimmunol.1800120.

"V体育安卓版" Invariant NKT Cells and Control of the Thymus Medulla

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Review

VSports在线直播 - Invariant NKT Cells and Control of the Thymus Medulla

Andrea J White et al. J Immunol. .

"V体育安卓版" Abstract

Most αβ T cells that form in the thymus are generated during mainstream conventional thymocyte development and involve the generation and selection of a diverse αβ TCR repertoire that recognizes self-peptide/MHC complexes. Additionally, the thymus also supports the production of T cell subsets that express αβ TCRs but display unique developmental and functional features distinct from conventional αβ T cells. These include multiple lineages of CD1d-restricted invariant NKT (iNKT) cells that express an invariant αβ TCR, branch off from mainstream thymocytes at the CD4+CD8+ stage, and are potent producers of polarizing cytokines. Importantly, and despite their differences, iNKT cells and conventional αβ T cells share common requirements for thymic epithelial microenvironments during their development. Moreover, emerging evidence suggests that constitutive cytokine production by iNKT cells influences both conventional thymocyte development and the intrathymic formation of additional innate CD8+ αβ T cells with memory-like properties VSports手机版. In this article, we review evidence for an intrathymic innate lymphocyte network in which iNKT cells play key roles in multiple aspects of thymus function. .

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VSports app下载 - Figures

Figure 1
Figure 1. Innate and Adaptive αβT-cell Development In The Thymus.
αβT-cells that are produced in the thymus are heterogeneous, and consist of multiple sublineages that are phenotypically and functionally distinct. Conventional αβT-cells, MAIT and iNKT-cells all derive from cortex-resident CD4+CD8+ (DP) thymocytes, with both MAIT and iNKT-cells being generated via TCR ligand recognition on thymocytes rather than cortical thymic epithelial cells (cTEC). The medulla represents an important microenvironment for both αβT-cells and iNKT-cells, where the latter regulate RANK-mediated mTEC development and the development of Eomesodermin+ CD8+ innate memory T-cells (TIM).
Figure 2
Figure 2. Cytokine Production By Intrathymic iNKT2 Cells Controls Conventional Thymocyte Egress Via The Type 2 IL4R.
In wildtype (WT) mice, IL4/IL13 production by type 2 iNKT-cells triggers Type 2 IL4R in signalling in mTEC for normal transit of fully mature conventional thymocytes from the medulla to the circulation via the perivascular space (PVS). While the downstream mediators of this process are not known, IL4Rα signalling in mTEC is known to trigger the expression of chemokines that include CXCL10 and CCL21. In IL4Rα-/- mice, lack of type 2 IL4R signalling in thymic stroma results in the intrathymic accumulation of mature thymocytes within the PVS, and a reduction in recent thymus emigrants (RTE).

References

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