Foxp3+ follicular regulatory T cells control T follicular helper cells and the germinal center response

By M. Linterman, Wim Pierson, S. K. Lee, A. Kallies, Shimpei Kawamoto, Tim F. Rayner, Monika Srivastava, D. Divekar, L. Beaton, Jennifer J. Hogan and 4 more. Nature Medicine, 2011

815 citations recorded by the source corpus.

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 the germinal center after immunization with protein antigens. These follicular regulatory T (TFR) cells share phenotypic characteristics with TFH and conventional Foxp3+ regulatory T (Treg) cells yet are distinct from both. Similar to TFH cells, TFR cell development depends on Bcl-6, SLAM-associated protein (SAP), CD28 and B cells; however, TFR cells originate from thymic-derived Foxp3+ precursors, not naive or TFH cells. TFR cells are suppressive in vitro and limit TFH cell and germinal center B cell numbers in vivo. In the absence of TFR cells, an outgrowth of non–antigen-specific B cells in germinal centers leads to fewer antigen-specific cells. Thus, the TFH differentiation pathway is co-opted by Treg cells to control the germinal center response.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/6b2c94554c679e5865fb032f496b0e03140e3a1d

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In Immunology

1. Naganari Ohkura
2. Shane Crotty
3. Shimon Sakaguchi
4. Y. Kitagawa
5. Alexander Y. Rudensky

Citations in the corpus

• T follicular helper cell differentiation, function, and roles in disease (2014, background): “The canonical secreted Tfh cell molecules are C-X-C motif chemokine 13 (CXCL13), IL-21, and IL-4 (Crotty, 2011; Kroenke et al., 2012; Liang et al., 2012; Linterman et al., 2011).”
• Development and maintenance of regulatory T cells. (2013, background): “Themain task of Foxp3+ nTreg cells is to migrate to inflammation sites and suppress various effector lymphocytes, especially helper T (Th) cell subsets: Th1, Th2, Th17, and follicular Th (Tfh) cells (Chaudhry et al., 2009; Chung et al., 2011; Koch et al., 2009; Linterman et al., 2011).”