Dataset Information

Role of NKG2a/c⁺CD8⁺ T cells in pathogenic versus non-pathogenic SIV infections.

ABSTRACT: Some viruses have established an equilibrium with their host. African green monkeys (AGM) display persistent high viral replication in the blood and intestine during Simian immunodeficiency virus (SIV) infection but resolve systemic inflammation after acute infection and lack intestinal immune or tissue damage during chronic infection. We show that NKG2_a/c ⁺CD8⁺ T cells increase in the blood and intestine of AGM in response to SIVagm infection in contrast to SIVmac infection in macaques, the latter modeling HIV infection. NKG2_a/c ⁺CD8⁺ T cells were not expanded in lymph nodes, and CXCR5⁺NKG2_a/c ⁺CD8⁺ T cell frequencies further decreased after SIV infection. Genome-wide transcriptome analysis of NKG2_a/c ⁺CD8⁺ T cells from AGM revealed the expression of NK cell receptors, and of molecules with cytotoxic effector, gut homing, and immunoregulatory and gut barrier function, including CD73. NKG2_a/c ⁺CD8⁺ T cells correlated negatively with IL-23 in the intestine during SIVmac infection. The data suggest a potential regulatory role of NKG2_a/c ⁺CD8⁺ T cells in intestinal inflammation during SIV/HIV infections.

SUBMITTER: Huot N

PROVIDER: S-EPMC8040270 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Role of NKG2a/c+CD8+ T cells in pathogenic versus non-pathogenic SIV infections.

Huot Nicolas N Rascle Philippe P Tchitchek Nicolas N Wimmer Benedikt B Passaes Caroline C Contreras Vanessa V Desjardins Delphine D Stahl-Hennig Christiane C Le Grand Roger R Saez-Cirion Asier A Jacquelin Beatrice B Müller-Trutwin Michaela M

iScience 20210315 4

Some viruses have established an equilibrium with their host. African green monkeys (AGM) display persistent high viral replication in the blood and intestine during Simian immunodeficiency virus (SIV) infection but resolve systemic inflammation after acute infection and lack intestinal immune or tissue damage during chronic infection. We show that NKG2a/c +CD8+ T cells increase in the blood and intestine of AGM in response to SIVagm infection in contrast to SIVm ...[more]

PMID: 33870131

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Project description:Background & aimsCD161-expressing CD8+ T cells consist of mucosal-associated invariant T cells with semi-invariant T-cell receptor (TCR) use and non-mucosal-associated invariant T CD161+CD8+ T cells with polyclonal TCR repertoire. Although CD161+CD8+ T cells are enriched in liver and embrace hepatitis B virus (HBV)-specific T cells in chronic hepatitis B (CHB) patients, their roles in disease progression remain poorly understood. This study aimed to decipher their profiling and dynamic changes during chronic HBV infection.MethodsBlood samples from 257 CHB patients and nontumor liver specimens from 73 HBV-positive patients were analyzed for CD161+CD8+ T-cell characterization by flow cytometry, TCR repertoire determination, transcriptomic analyses, and cell experiments.ResultsCD161+CD8+ T cells were increased and hyperactivated in patients, while positive correlation between the CD161+CD8+ T-cell ratio and HBV-DNA level suggested this was insufficient to control HBV replication. The overlap of complementarity determining region 3 sequences supported the switch between CD161-CD8+ and CD161+CD8+ populations. Although CD161+CD8+ T cells were endowed with innateness phenotype and enhanced antiviral capacity, the population from patients had impaired type I cytokine production, and increased interleukin 17 and granzyme B secretion. The increased CD161+CD8+ T cells and their increased granzyme B secretion correlated positively with inflammation-associated liver injury. Hepatic CD161+CD8+ T cells showed neutrophil-related pathogenic potential because they had increased transcript signatures and proinflammatory cytokine production in neutrophil recruitment- and response-related pathways that changed consistently in the injured liver.ConclusionsOur results highlight the reduced antiviral potency but increased pathogenic potential of CD161+CD8+ T cells in CHB patients, supporting CD161 expression as a marker of pathogenic CD8+ T subset and the intervention target for liver injury.

Dataset Information

Role of NKG2a/c⁺CD8⁺ T cells in pathogenic versus non-pathogenic SIV infections.

Publications

Role of NKG2a/c<sup>+</sup>CD8<sup>+</sup> T cells in pathogenic versus non-pathogenic SIV infections.

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