IL-6 promotes the differentiation of a subset of naive CD8+ T cells into IL-21–producing B helper CD8+ T cells

Yang, Rui; Masters, April R.; Fortner, Karen A.; Champagne, Devin P.; Yanguas‐Casás, Natalia; Silberger, Daniel J.; Weaver, Casey T.; Haynes, Laura; Rincón, Mercedes

doi:10.1084/jem.20160417

Cited by 116 publications

(113 citation statements)

References 40 publications

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“…The existing evidence has shown an uncontemplated role of CD8 + T cells in providing help for humoral immunity. 29,30 Of the cytokines we assessed, IL-21 is of great interest as it is pivotal for antibody production. Our previous work has verified that IL-21 represents a major mediator of the beneficial function of CXCR5 + CD4 + T cells in promoting the generation of antibody to HBeAg.…”

Section: Discussionmentioning

confidence: 99%

CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection

Tang

Guo

et al. 2020

Journal of Hepatology

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Highlights CXCR5 + CD8 + T cells produce higher levels of HBV-specific IFN-c and IL-21 than CXCR5 À CD8 + T cells. CXCR5 + CD8 + T cells retain functional capacity in inhibiting HBV replication and supporting B cell antibody production. PD1 blockade and exogenous IL-21 enhance production of IFN-c from CXCR5 + CD8 + T cells. High expression of intrahepatic CXCL13 facilitates CXCR5 +-CD8 + T cell recruitment and promotes immune control of HBV.

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Section: Discussionmentioning

confidence: 99%

CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection

Tang

Guo

et al. 2020

Journal of Hepatology

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“…Specifically, Dienz and colleagues (37) reported that IL-6 2/2 mice succumbed to sublethal doses of influenza A H1N1 in association with apoptosis of antiviral neutrophils in the lung, whereas Lauder and colleagues (38) found that infection of IL-6 2/2 mice with influenza A H1N1 resulted in infiltration of the lungs with monocytes in association with progression to pulmonary edema and respiratory distress due to an inefficient antiviral T cell response. Subsequent studies that focused on the roles of CD4 + T cells, cytotoxic CD8 + T cells, and IL-27, IL-21, and Ab production as well as lung repair mechanisms (39)(40)(41)(42) all identified IL-6 as a protective factor in acute influenza infection.…”

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confidence: 99%

Critical Adverse Impact of IL-6 in Acute Pneumovirus Infection

Percopo

Brenner

et al. 2019

The Journal of Immunology

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C.M.P. designed and performed experiments and reviewed first and subsequent drafts of the manuscript; M.M. performed experiments for the revised manuscript, assessed experimental outcomes, evaluated data for publication, and reviewed first and subsequent drafts of the manuscript; T.A.B. designed and performed experiments and reviewed first and subsequent drafts of the manuscript; J.O.K. designed and performed experiments involving infection with rK2-PVM and reviewed first and subsequent drafts of the manuscript; T.J.B. provided critical assistance in designing flow cytometric protocols and reviewed first and subsequent drafts of the manuscript; K.L. provided critical assistance for evaluation of T cells and T cell subsets and reviewed manuscript revision prior to publication; H.F.R. conceptualized the study, performed experiments, evaluated data, and generated the first and subsequent drafts of the written manuscript.

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“…areas represent immunologically privileged areas with limited presence of potential CTLs(Connick et al, 2007). Besides their cytolytic activity, fCD8 cells can promote isotype switching of B cells in the settings of autoimmunity(Valentine et al, 2018) while IL-6, a positive regulator of Tfh cells(Eto et al, 2011), can also induce IL21-producing CD8 T cells with follicular helper function(Yang et al, 2016) and therefore further induce humoral responses indirectly through local IL21 production. Despite a trend for higher baseline CD3 hi CD4 lo T cells in old compared to young LNs, a significant positive correlation between Tfh and CD3 hi CD4 lo was found only in young animals, indicating a possible "helper" fCD8 T-cell function in young NHPs.Tissue inflammation and immune activation may play a significant role in follicular immunodynamics(Ferrando-Martinez et al, 2018).…”

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confidence: 99%

Compromised steady‐state germinal center activity with age in nonhuman primates

et al. 2019

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Age-related reductions in vaccine-induced B cells in aging indicate that germinalcenters (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1 hi CD4 T (Tfh) and proliferating (Ki67 hi ) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3 hi Lag3 hi CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals.Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging.Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging.

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IL-6 promotes the differentiation of a subset of naive CD8+ T cells into IL-21–producing B helper CD8+ T cells

Abstract: IL-6 promotes the differentiation of a subset of naïve CD8+ T cells into IL-21–producing B helper CD8+ T cells.

Cited by 116 publications

References 40 publications

CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection

CXCL13-mediated recruitment of intrahepatic CXCR5+CD8+ T cells favors viral control in chronic HBV infection

Critical Adverse Impact of IL-6 in Acute Pneumovirus Infection

Compromised steady‐state germinal center activity with age in nonhuman primates

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