Maturation and Emigration of Single-Positive Thymocytes

Xu, Xi; Zhang, Shusong; Li, Pingping; Lu, Jin; Xuan, Qun; Ge, Qing

doi:10.1155/2013/282870

Cited by 26 publications

(19 citation statements)

References 147 publications

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“…are upregulated while others such as CD24 are down-regulated as DP cells mature into SP thymocytes32. Initially, the expression of CD24 and CD3 was analyzed on CD8 + SP cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma

Majumdar

Deobagkar-Lele

Adiga

et al. 2017

Sci Rep

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The thymus is known to atrophy during infections; however, a systematic study of changes in thymocyte subpopulations has not been performed. This aspect was investigated, using multi-color flow cytometry, during oral infection of mice with Salmonella Typhimurium (S. Typhimurium). The major highlights are: First, a block in the developmental pathway of CD4−CD8− double negative (DN) thymocytes is observed. Second, CD4+CD8+ double positive (DP) thymocytes, mainly in the DP1 (CD5loCD3lo) and DP2 (CD5hiCD3int), but not DP3 (CD5intCD3hi), subsets are reduced. Third, single positive (SP) thymocytes are more resistant to depletion but their maturation is delayed, leading to accumulation of CD24hiCD3hi SP. Kinetic studies during infection demonstrated differences in sensitivity of thymic subpopulations: Immature single positive (ISP) > DP1, DP2 > DN3, DN4 > DN2 > CD4+ > CD8+. Upon infection, glucocorticoids (GC), inflammatory cytokines, e.g. Ifnγ, etc are induced, which enhance thymocyte death. Treatment with RU486, the GC receptor antagonist, increases the survival of most thymic subsets during infection. Studies with Ifnγ−/− mice demonstrated that endogenous Ifnγ produced during infection enhances the depletion of DN2-DN4 subsets, promotes the accumulation of DP3 and delays the maturation of SP thymocytes. The implications of these observations on host cellular responses during infections are discussed.

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“…are upregulated while others such as CD24 are down-regulated as DP cells mature into SP thymocytes32. Initially, the expression of CD24 and CD3 was analyzed on CD8 + SP cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma

Majumdar

Deobagkar-Lele

Adiga

et al. 2017

Sci Rep

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“…This is in contrast to fully mature SP thymocytes and thymic emigrants, which proliferate when triggered through the TCR. Subsequently, other groups have shown that a number of other cell surface proteins, including CD69 and various cytokine and chemokine receptors, change dramatically during maturation (Table I) (5–7). Mice expressing GFP under the control of the RAG1 or RAG2 regulatory elements have been instrumental in defining the temporal order of phenotypic changes during maturation, as RAG gene transcription is high in DP thymocytes, but acutely terminated upon positive selection.…”

Section: Acquiring the Competence To Dividementioning

confidence: 99%

T Cell Adolescence: Maturation Events Beyond Positive Selection

Hogquist

Xing

Hsu

et al. 2015

The Journal of Immunology

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Single positive (SP) thymocytes that successfully complete positive and negative selection must still undergo one final step, generally termed T cell maturation, before they gain functional competency and enter the long-lived T cell pool. Maturation initiates after positive selection in SP thymocytes, and continues in the periphery in recent thymic emigrants (RTEs), before these newly produced T cells gain functional competency and are ready to participate in the immune response as peripheral naïve T cells. Recent work using genetically altered mice demonstrates that T cell maturation is not a single process, but a series of steps that occur independently and sequentially after positive selection. This review will focus on the changes that occur during T maturation, and the molecules and pathways that are critical at each step.

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“…Thymocytes that express a TCR with strong affinity to self-peptide presented by MHC die by negative selection (14). Positively selecting thymocytes undergo CD4-versus-CD8 lineage commitment (16), maturation (17, 18), and exit the thymus to become peripheral CD4 and CD8 T cells.…”

Section: Introductionmentioning

confidence: 99%

HDAC3 Is Required for the Downregulation of RORγt during Thymocyte Positive Selection

Philips

Chen

McWilliams

et al. 2016

The Journal of Immunology

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To generate functional peripheral T cells, proper gene regulation during T cell development is critical. Here, we found that histone deacetylase 3 (HDAC3) is required for T cell development. T cell development in CD2-icre HDAC3 conditional knockout mice (HDAC3-cKO) was blocked at positive selection, resulting in few CD4 and CD8 T cells, and could not be rescued by a TCR-transgene. These SP thymocytes failed to upregulate Bcl-2, leading to increased apoptosis. HDAC3-cKO mice failed to downregulate RORγt during positive selection, and phenocopied the block in positive selection in RORγt-transgenic mice. In the absence of HDAC3, the RORC promoter was hyperacetylated. In the periphery, the few CD4 T cells present were skewed towards RORγt+ IL-17-producing Th17 cells, leading to inflammatory bowel disease. Positive selection of CD8SP thymocytes was restored in RORγt-KO Bcl-xl-transgenic HDAC3-cKO mice, demonstrating that HDAC3 is required at positive selection to down-regulate RORγt.

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Maturation and Emigration of Single-Positive Thymocytes

Cited by 26 publications

References 147 publications

Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma

Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma

T Cell Adolescence: Maturation Events Beyond Positive Selection

HDAC3 Is Required for the Downregulation of RORγt during Thymocyte Positive Selection

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