Nature immunology · 2016
CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Leong Yew Ann, Chen Yaping, Ong Hong Sheng, Wu Di, Man Kevin, Deleage Claire, Minnich Martina, Meckiff Benjamin J, Wei Yunbo, Hou Zhaohua, Zotos Dimitra, Fenix Kevin A, Atnerkar Anurag, Preston Simon, Chipman Jeffrey G, Beilman Greg J, Allison Cody C, Sun Lei, Wang Peng, Xu Jiawei, Toe Jesse G, Lu Hao K, Tao Yong, Palendira Umaimainthan, Dent Alexander L, Landay Alan L, Pellegrini Marc, Comerford Iain, McColl Shaun R, Schacker Timothy W, Long Heather M, Estes Jacob D, Busslinger Meinrad, Belz Gabrielle T, Lewin Sharon R, Kallies Axel, Yu Di
Аннотация
During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC cell development. The identification of TFC cells has far-reaching implications for the development of strategies to control infections that target B cells and TFH cells and to treat B cell-derived malignancies.
Предметные рубрики MeSH
AnimalsArenaviridae InfectionsB-LymphocytesBasic Helix-Loop-Helix ProteinsCell DifferentiationCells, CulturedEpstein-Barr Virus InfectionsGene Expression RegulationGerminal CenterHIVHepatocyte Nuclear Factor 1-alphaHumansLymphocytic choriomeningitis virusMaleMiceMice, Inbred C57BLMice, TransgenicPositive Regulatory Domain I-Binding Factor 1Proto-Oncogene Proteins c-bcl-6Receptors, CXCR5T-Lymphocytes, CytotoxicTranscription Factors