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Foxp3+ follicular regulatory T cells control the germinal center response.
- Source :
- Nature Medicine; Aug2011, Vol. 17 Issue 8, p975-982, 8p, 6 Graphs
- Publication Year :
- 2011
-
Abstract
- Follicular helper (T<subscript>FH</subscript>) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of T<subscript>FH</subscript> numbers maintains self tolerance. We describe a population of Foxp3<superscript>+</superscript>Blimp-1<superscript>+</superscript>CD4<superscript>+</superscript> T cells constituting 10-25% of the CXCR5<superscript>high</superscript>PD-1<superscript>high</superscript>CD4<superscript>+</superscript> T cells found in the germinal center after immunization with protein antigens. These follicular regulatory T (T<subscript>FR</subscript>) cells share phenotypic characteristics with T<subscript>FH</subscript> and conventional Foxp3<superscript>+</superscript> regulatory T (T<subscript>reg</subscript>) cells yet are distinct from both. Similar to T<subscript>FH</subscript> cells, T<subscript>FR</subscript> cell development depends on Bcl-6, SLAM-associated protein (SAP), CD28 and B cells; however, T<subscript>FR</subscript> cells originate from thymic-derived Foxp3<superscript>+</superscript> precursors, not naive or T<subscript>FH</subscript> cells. T<subscript>FR</subscript> cells are suppressive in vitro and limit T<subscript>FH</subscript> cell and germinal center B cell numbers in vivo. In the absence of T<subscript>FR</subscript> cells, an outgrowth of non-antigen-specific B cells in germinal centers leads to fewer antigen-specific cells. Thus, the T<subscript>FH</subscript> differentiation pathway is co-opted by T<subscript>reg</subscript> cells to control the germinal center response. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cells
GERMINAL centers
ANTIGENS
PROTEINS
B cells
Subjects
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 17
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 63714124
- Full Text :
- https://doi.org/10.1038/nm.2425