Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

CXCR5+ Follicular Cytotoxic T cells Control Viral Infection in B Cell follicles

ABSTRACT: Lymphocytic Choriomeningitis Virus (LCMV) specific CD8+ T cells (P14) were transferred into congenic WT mice followed by LCMV(DOCILE) infection. CXCR5-expressing (CXCR5+) or CXCR5 non-expressing (CXCR5-) P14 were purified on day 8 after infection, and total mRNA were sequenced from these populations. mRNA of P14 from uninfected mice (Naive P14) was also sequenced. Examination of mRNA level in CXCR5 expressing P14 (CXCR5+P14) and non-expressing P14 (CXCR5-P14) from LCMV infected mice day 8 post infection. mRNA of P14 from uninfected mice (NaÃ¯ve P14) was also examined.

ORGANISM(S): Mus musculus

SUBMITTER: Yew Ann Leong

PROVIDER: E-GEOD-76279 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles.

Leong Yew Ann YA Chen Yaping Y Ong Hong Sheng HS Wu Di D Man Kevin K Deleage Claire C Minnich Martina M Meckiff Benjamin J BJ Wei Yunbo Y Hou Zhaohua Z Zotos Dimitra D Fenix Kevin A KA Atnerkar Anurag A Preston Simon S Chipman Jeffrey G JG Beilman Greg J GJ Allison Cody C CC Sun Lei L Wang Peng P Xu Jiawei J Toe Jesse G JG Lu Hao K HK Tao Yong Y Palendira Umaimainthan U Dent Alexander L AL Landay Alan L AL Pellegrini Marc M Comerford Iain I McColl Shaun R SR Schacker Timothy W TW Long Heather M HM Estes Jacob D JD Busslinger Meinrad M Belz Gabrielle T GT Lewin Sharon R SR Kallies Axel A Yu Di D

Nature immunology 20160803 10

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 differ ...[more]

PMID: 27487330

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Project description:CD8+ T-cells inhibit virus replication in SIV-infected rhesus macaques (RM). However, it is not clear how SIV infection is controlled in germinal center during chronic SIV infection and limited information exists on the characteristics of CXCR5+ CD8 T cells during chronic SIV/HIV infection. In this study, we used functional genomics to investigate characteristic features and potential mechanisms of CXCR5+ and CXCR5- SIV specific CD8 T cells for the control of pathogenic SIV infection. Six chronically SIV infected RMs, three SIVE660 infected and three SIV mac251 infected that are positive for Mamu A01 allele were selected and SIV-specific CXCR5+ and CXCR5- CD8 T cells were sorted based on CXCR5 expression. RNA from sorted cells were extracted and microarray were performed and analysed. Principal component analysis demonstrated that overall gene expression difference between CXCR5+ and CXCR5- SIV-specific CD8 T cells. Interestingly, the CXCR5+ CD8 T cells revealed a distinct gene signature pattern when compared to CXCR5- CD8 T cells. Unlike the CXCR5- CD8 T cells, the CXCR5+ CD8 T cells expressed higher levels of genes associated with Tfh CD4 T cells such as the master transcription factor Bcl6, CD200, and CTLA4 as well as markers associated with Th2 CD4 T cells such as IL-4R (CD124), CCR4, STAT6, NFATC, and IL-10. Effector molecules typically observed in cytotoxic CD8 T cells such as granzyme A, B, and K were expressed at lower levels on CXCR5+ CD8 T cells compared to their CXCR5- counterparts. CXCR5+ CD8 T cells also expressed higher levels of molecules associated with co-stimulation/antigen presentation such as CD40, CD83, 41BBL and MAMU-DRA. The CXCR5+ CD8 also expressed higher levels of inhibitory receptors such as CD200 and SPRY2 but lower levels of other inhibitory receptors CD160 and CD244. The functional consequence of the expression of these molecules is yet to be determined. Additionally, CXCR5+ CD8 T cells expressed higher levels of the anti-apoptotic gene Bcl-2 and lower levels of the pro-apoptotic gene annexin, suggestive of their better survival potential during chronic SIV infection. Collectively, these results demonstrate that SIV specific CXCR5+ CD8 T cells possess a unique gene expression signature compared to SIV-specific CXCR5- CD8 T cells.

Dataset Information

CXCR5+ Follicular Cytotoxic T cells Control Viral Infection in B Cell follicles

Publications

CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles.

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