Immune Activation Is Associated with CD8 T Cell Interleukin-21 Production in HIV-1-Infected Individuals

Williams, LaTonya D.; Amatya, Nilesh; Bansal, Anju; Sabbaj, Steffanie; Heath, Sonya L.; Sereti, Irini

doi:10.1128/jvi.00764-14

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…It had been demonstrated that IL-21 is produced by CD4 + but not CD8 + T cells in both Crohn’s disease and ulcerative colitis patients 24 . CD8 + T cells from HIV-1-infected individuals can produce IL-21, and IL-21-producing CD8 + T cells are associated with high activation levels 25 . In polyp tissues, we found that both CD4 + and CD8 + T cells produced IL-21 at higher levels than in control tissues 15 .…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characteristics of IL-21-expressing CD8+ T cells in human nasal polyps

Xiao

Jia

Bai

et al. 2016

Sci Rep

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Although CD4+ T cells are recognized to play an important role in the inflammatory response of nasal polyps (NPs), the biological functions of CD8+ T cells in polypogenesis remain unclear. In this study, we analyzed cell markers, cytokine expression and transcription factors in IL-21-expressing CD8+ T cells in polyp tissues of NP patients. The results showed that the majority of IL-21-producing CD8+ T cells were effector memory cells and they co-expressed IFN-γ. IL-21-expressing CD8+ T cells in polyp tissues expressed higher CXCR5, PD-1, and ICOS levels than cells in control tissues and showed significantly higher T-bet and Bcl-6 expression levels compared with IL-21−CD8+ T cells. Purified polyp CD8+ T cells promoted IgG production from isolated polyp B cells in vitro, and recombinant IL-12 modulated the expression of IL-21, IFN-γ and CD40L in purified polyp CD8+ T cells. Moreover, the percentage of IL-21+CD8+ T cells in polyp tissues was positively correlated with endoscopic and CT scan scores in NP patients. These findings indicated that polyp CD8+ T cells, by co-expressing IL-21 and IFN-γ and other markers, display a Tfh cell functionality, which is associated with the clinical severity of NP patients.

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Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characteristics of IL-21-expressing CD8+ T cells in human nasal polyps

Xiao

Jia

Bai

et al. 2016

Sci Rep

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“…Among different disease-status groups of HIV-infected patients, only the elite controllers maintain normal production of IL-21, and IL-21-producing CD4 + T cells are decreased in HIV-infected viremic patients or patients with progressive disease 84 , 85 . Interestingly, CD8 + T cells in HIV-infected patients produce IL-21, and the frequencies of these cells are closely associated with viral control 86 , 87 , suggesting that the loss of IL-21 production correlates with disease progression. Correspondingly, recent studies showed that T follicular helper (Tfh) cells, which are the major source of IL-21, are the most efficiently infected by HIV among different CD4 + T-cell subtypes 88 , and defective Tfh function results in impaired humoral immunity against HIV 89 .…”

Section: Il-21 As a Potential Vaccine Adjuvantmentioning

confidence: 99%

IL-21 Signaling in Immunity

2016

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IL-21 is a type I cytokine produced by T cells and natural killer T cells that has pleiotropic actions on a wide range of immune and non-immune cell types. Since its discovery in 2000, extensive studies on the biological actions of IL-21 have been performed in vitro and in vivo. Recent reports describing patients with primary immunodeficiency caused by mutations of IL21 or IL21R have further deepened our knowledge of the role of this cytokine in host defense. Elucidation of the molecular mechanisms that mediate IL-21’s actions has provided the rationale for targeting IL-21 and IL-21 downstream mediators for therapeutic purposes. The use of next-generation sequencing technology has provided further insights into the complexity of IL-21 signaling and has identified transcription factors and co-factors involved in mediating the actions of this cytokine. In this review, we discuss recent advances in the biology and signaling of IL-21 and how this knowledge can be potentially translated into clinical settings.

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“…Instead, Williams et al . have indicated that IL-21 production by CD8 + T cells was associated with high levels of activation [ 33 ]. Moreover, other studies have found that IL-21 is produced by NKT cells [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis-Specific IL-21+IFN-γ+CD4+ T Cells Are Regulated by IL-12

Jiang

Lao

et al. 2016

PLoS ONE

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In the current study of Mycobacterium tuberculosis (MTB)-specific T and B cells, we found that MTB-specific peptides from early secreted antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) induced the expression of IL-21 predominantly in CD4+ T cells. A fraction of IL-21-expressing CD4+ T cells simultaneously expressed Th1 cytokines but did not secrete Th2 or Th17 cytokines, suggesting that MTB-specific IL-21-expressing CD4+ T cells were different from Th1, Th2 and Th17 subpopulations. The majority of MTB-specific IL-21-expressing CD4+ T cells co-expressed IFN-γ and IL-21+IFN-γ+CD4+ T cells exhibited obviously polyfunctionality. In addition, MTB-specific IL-21-expressing CD4+ T cells displayed a CD45RO+CD62LlowCCR7lowCD40LhighICOShigh phenotype. Bcl-6-expression was significantly higher in IL-21-expressing CD4+ T cells than IL-21-CD4+ T cells. Moreover, IL-12 could up-regulate MTB-specific IL-21 expression, especially the frequency of IL-21+IFN-γ+CD4+ T cells. Taken together, our results demonstrated that MTB-specific IL-21+IFN-γ+CD4+ T cells from local sites of tuberculosis (TB) infection could be enhanced by IL-12, which have the features of both Tfh and Th1 cells and may have an important role in local immune responses against TB infection.

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Immune Activation Is Associated with CD8 T Cell Interleukin-21 Production in HIV-1-Infected Individuals

Cited by 9 publications

References 30 publications

Phenotypic and functional characteristics of IL-21-expressing CD8+ T cells in human nasal polyps

Phenotypic and functional characteristics of IL-21-expressing CD8+ T cells in human nasal polyps

IL-21 Signaling in Immunity

Mycobacterium tuberculosis-Specific IL-21+IFN-γ+CD4+ T Cells Are Regulated by IL-12

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