Yu, DiYe, Lilin2022-11-301471-4906http://hdl.handle.net/1885/281395CD8+ T cells differentiate into multiple effector and memory subsets to carry out immune clearance of infected and cancerous cells and provide long-term protection. Recent research identified a CXCR5+Tcf1+Tim-3− subset that localizes in, or proximal to, B cell follicles in secondary lymphoid organs of mice, non-human primates, and humans, hereby termed follicular cytotoxic T (TFC) cells. With remarkable similarity to follicular helper T (TFH) cells, TFC differentiation is dependent on transcription factors E2A, Bcl6, and Tcf1, but inhibited by other regulators, including Blimp1, Id2, and Id3. This review summarizes the phenotype, function, and differentiation of this new subset. Owing to its follicular location and self-renewal capability, we propose immunotherapeutic strategies to target TFC cells to potentially treat certain cancers and chronic infections such as HIV-1.This work was supported by Australian National Health and Medical Research Council (GNT1147709 to D.Y.), the National Key Research and Development Program of China (2017YFC0909003 to D.Y.), the amfAR Research Consortium on HIV Eradication (109327-59-RGRL to D. Y), the Shandong Provincial Natural Science Foundation (ZR2016YL013 to D.Y.) and Priority Research Program of Shandong Academy of Sciences (D.Y.). D.Y. is supported by the Bellberry-Viertel Senior Medical Research Fellowship and intramural funds from The Australian National University, Shandong Academy of Sciences and Renji Hospitaapplication/pdfen-AU© 2018 Elsevier Ltd.201810.1016/j.it.2018.10.0022021-11-28