CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles.
Yew Ann LeongYaping ChenHong Sheng OngDi WuKevin ManClaire DeleageMartina MinnichBenjamin J MeckiffYunbo WeiZhaohua HouDimitra ZotosKevin A FenixAnurag AtnerkarSimon PrestonJeffrey G ChipmanGreg J BeilmanCody C AllisonLei SunPeng WangJiawei XuJesse G ToeHao K LuYong TaoUmaimainthan PalendiraAlexander L DentAlan L LandayMarc PellegriniIain ComerfordShaun R McCollTimothy W SchackerHeather M LongJacob D EstesMeinrad BusslingerGabrielle T BelzSharon R LewinAxel KalliesDi YuPublished in: Nature immunology (2016)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- human immunodeficiency virus
- epstein barr virus
- transcription factor
- stem cells
- endoplasmic reticulum stress
- cell death
- gene expression
- palliative care
- oxidative stress
- signaling pathway
- hiv infected
- dendritic cells
- bone marrow
- poor prognosis
- regulatory t cells
- mesenchymal stem cells
- single cell
- binding protein
- dna binding