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Thymocyte development

The identification of THEMIS

Nature Reviews Immunology volume 9, pages 604–605 (2009)Cite this article

Thymocytes progress through various linear developmental stages before their commitment to either CD4 or CD8 single positive (SP) T cells. T cell receptor (TCR) signalling is known to be important at each of these developmental stages, but the exact signalling pathways that control the transition from double positive (DP) to SP thymocytes and CD4 versus CD8 lineage choice (a process known as positive selection) are not completely understood. Therefore, the authors searched for new genes that might have a role in T cell development and the three groups independently identified THEMIS. Themis mRNA is expressed mainly in the thymus (and to a lesser extent in the spleen and lymph nodes) and is expressed by all thymocytes and mature T cells but not by B cells or natural killer cells. Themis expression is highest in DP thymocytes and is downregulated in SP thymocytes and peripheral T cells, suggesting a specific role for THEMIS in the DP to SP development stage.

To further understand the role of THEMIS in thymocyte development, the three groups made use of gene-targeted or ethylnitrosourea (ENU)-induced THEMIS-deficient mice. These mice developed normally and had no obvious abnormalities. However, the number of mature SP T cells, especially CD4 SP T cells, was significantly lower in these mice than in control mice. By contrast, the DP thymocyte population was larger than in control mice, indicating a defect in positive selection in the absence of THEMIS. Two of the studies also identified a defect in negative selection in Themis−/− mice and all three studies showed that the defect in late thymocyte development was T cell intrinsic. Because TCR signals are known to be required for positive selection, the data suggest that THEMIS might have a role in TCR signal transduction.

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ORIGINAL RESEARCH PAPERS

  1. Fu, G. et al. Themis controls thymocyte selection through regulation of T cell antigen receptor–mediated signaling. Nature Immunol. 10, 848–856 (2009)

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  2. Lesourne, R. et al. Themis, a T cell–specific protein important for late thymocyte development. Nature Immunol. 10, 840–847 (2009)

    Article  CAS  Google Scholar 

  3. Johnson, A. L. et al. Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection. Nature Immunol. 10, 831–839 (2009)

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Authors
  1. Olive Leavy
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Leavy, O. The identification of THEMIS. Nat Rev Immunol 9, 604–605 (2009). https://doi.org/10.1038/nri2624

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