| Autor: |
Hendrik eZiegler, Christian eWelker, Marco eSterk, Jan eHaarer, Hans-Georg eRammensee, Rupert eHandgretinger, Karin eSchilbach |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 5 (2014) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2014.00645 |
| Popis: |
The lifelong generation of alpha beta T cells enables us to continuously build immunity against pathogens and malignancies despite the loss of thymic function with age. Consequently, alpha beta T-cell development has to occur independently of the thymus. However, the sites and mechanisms of extrathymic T-cell development are not yet understood in detail. gamma delta T cells represent a small fraction of the overall T-cell pool, and are endowed with tremendous phenotypic and functional plasticity. gamma delta T cells that express the Vdelta1 gene segment are a minor population in human peripheral blood but predominate in epithelial (and inflamed) tissues. Here, we characterize a peripheral Vdelta1+ gamma delta T-cell subpopulation that expresses stem-cell and progenitor markers and is able to develop into functional alpha beta 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 reorganization of the Vdelta1+ gamma delta TCR into the alpha beta TCR as a consequence of TCR-gamma chain downregulation and the expression of surface Vdelta1+Vbeta+ 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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