Foxp3+ follicular regulatory T cells control T follicular helper cells and the germinal center response
| Autor: | Linterman, Michelle A., Pierson, Wim, Lee, Sau K., Kallies, Axel, Kawamoto, Shimpei, Rayner, Tim F., Srivastava, Monika, Divekar, Devina P., Beaton, Laura, Hogan, Jennifer J., Fagarasan, Sidonia, Liston, Adrian, Smith, Kenneth G. C., Vinuesa, Carola G. |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | Nature medicine |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Follicular helper (TFH) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of TFH numbers maintains self-tolerance. We describe a population of Foxp3+Blimp-1+CD4+ T cells constituting 10-25% of the CXCR5highPD-1highCD4+ T cells found in germinal center after immunization. These follicular regulatory T cells (TFR) share phenotypic characteristics with TFH and conventional Foxp3+ regulatory T cells (Treg) yet are distinct from either. Similar to TFH cells, TFR development depends on Bcl-6, SAP, CD28 and B cells; however TFR originate from thymic-derived Foxp3+ precursors, not naïve or TFH cells. TFR are suppressive in vitro and limit TFH and germinal center B cell numbers in vivo. In the absence of TFR, an outgrowth of non-antigen-specific B cells in germinal centers leads to fewer antigen-specific cells. Thus, Treg cells use the TFH differentiation pathway to produce specialized suppressor cells that control the germinal center response. |
| Databáze: | OpenAIRE |
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