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. 2019 Dec 13;10:2918. doi: 10.3389/fimmu.2019.02918

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Copyright © 2019 Gong, Zheng and Zhou.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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T_FH cell and related subsets in secondary lymph organs and in peripheral circulation. In secondary lymphoid organs, T follicular helper (T_FH) cells are composed of subsets with distinct phenotypes. These subsets include pre-T_FH cells, germinal center (GC) T_FH cells, and memory T_FH cells. Through the upregulation of programmed cell death protein 1 (PD-1) and CXC-chemokine receptor 5 (CXCR5), regulatory T (T_reg) cells migrate into B cell follicles and become immature T follicular regulatory (T_FR) cells and germinal center T_FR cells. In the peripheral circulation, circulating T_FH (cT_FH) cells can be categorized into effector memory (cT_FH−EM) cells and central memory (cT_FH−CM) cells on the basis of the expression of PD-1 and CC-chemokine receptor 7 (CCR7). cT_FH cells can also be sub-grouped into cT_FH1, cT_FH2, cT_FH13, and cT_FH17 cells on the basis of the differential expression of CXCR3 and CCR6 as well as the secretion of interleukin-4 (IL-4) and IL-13. Circulating T_FR cells are similar to T_reg cells but express CXCR5. Notably, T peripheral helper (T_PH) cells do not express CXCR5 but can produce IL-21 and CXCL13, which allows them to provide help to B cells.