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Human Peripheral CD4(+) V?1(+) ??T Cells Can Develop into ??T Cells.


ABSTRACT: The lifelong generation of ??T cells enables us to continuously build immunity against pathogens and malignancies despite the loss of thymic function with age. Homeostatic proliferation of post-thymic naïve and memory T cells and their transition into effector and long-lived memory cells balance the decreasing output of naïve T cells, and recent research suggests that also ??T-cell development independent from the thymus may occur. However, the sites and mechanisms of extrathymic T-cell development are not yet understood in detail. ??T cells represent a small fraction of the overall T-cell pool, and are endowed with tremendous phenotypic and functional plasticity. ??T cells that express the V?1 gene segment are a minor population in human peripheral blood but predominate in epithelial (and inflamed) tissues. Here, we characterize a CD4(+) peripheral V?1(+) ??T-cell subpopulation that expresses stem-cell and progenitor markers and is able to develop into functional ??T cells ex vivo in a simple culture system and in vivo. The route taken by this process resembles thymic T-cell development. However, it involves the re-organization of the V?1(+) ??TCR into the ??TCR as a consequence of TCR-? chain downregulation and the expression of surface V?1(+)V?(+) TCR components, which we believe function as surrogate pre-TCR. This transdifferentiation process is readily detectable in vivo in inflamed tissue. Our study provides a conceptual framework for extrathymic T-cell development and opens up a new vista in immunology that requires adaptive immune responses in infection, autoimmunity, and cancer to be reconsidered.

SUBMITTER: Ziegler H 

PROVIDER: S-EPMC4329445 | BioStudies | 2014-01-01T00:00:00Z

REPOSITORIES: biostudies

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