Human Memory, but Not Naive, CD4+ T Cells Expressing Transcription Factor T-bet Might Drive Rapid Cytokine Production

Yu, S.; Zhang, Yannan; Yang, Baofeng; Wu, Changyou

doi:10.1074/jbc.m114.608745

Cited by 20 publications

(15 citation statements)

References 30 publications

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“…While we ideally would have included the antibody against IFNγ in our evaluation of functional differences between purposed memory subsets, unfortunately the limited variety of available fluorochrome conjugates prohibited this. TNFα does however appear to be differentially expressed by human naïve and memory T cells after a similar brief in vitro stimulation period, although expression in murine memory T cell subsets is somewhat less discriminating(von Fliedner et al, 1992; Yu et al, 2014). In addition, further functional characterization of these subsets by evaluation of their proliferative capacity, cytotoxic potential, and production of cytokines such as IL2, are also necessary in the future(Brenchley et al, 2002; Geginat et al, 2001; Ohshima et al, 1999; Seder et al, 2008).…”

Section: Discussionmentioning

confidence: 91%

Multi-color flow cytometry for evaluating age-related changes in memory lymphocyte subsets in dogs

Withers

Moore

Chang

et al. 2018

Developmental & Comparative Immunology

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While dogs are increasingly being utilized as large-animal models of disease, important features of age-related immunosenescence in the dog have yet to be evaluated due to the lack of defined naïve vs. memory T lymphocyte phenotypes. We therefore performed multi-color flow cytometry on peripheral blood mononuclear cells from young and aged beagles, and determined the differential cytokine production by proposed memory subsets. CD4+ and CD8+ T lymphocytes in aged dogs displayed increased cytokine production, and decreased proliferative capacity. Antibodies targeting CD45RA and CD62L, but less so CD28 or CD44, defined canine cells that consistently exhibited properties of naïve-, central memory-, effector memory-, and terminal effector-like CD4+ and CD8+ T lymphocyte subsets. Older dogs demonstrated decreased frequencies of naïve-like CD4+ and CD8+ T lymphocytes, and an increased frequency of terminal effector-like CD8+ T lymphocytes. Overall findings revealed that aged dogs displayed features of immunosenescence similar to those reported in other species.

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Section: Discussionmentioning

confidence: 91%

Multi-color flow cytometry for evaluating age-related changes in memory lymphocyte subsets in dogs

Withers

Moore

Chang

et al. 2018

Developmental & Comparative Immunology

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“…CD4+ CTL express part of the CD8 T cell lineage transcriptional program ( 10 ). Both CD4+ and CD8+ CTLs express, e.g., T-bet, Eomes, Runx3, and Hobit at higher levels compared to their naïve counterparts ( 57 – 60 ). Investigating the pathways involved in the formation of these cells could identify precursor cells defined by the expression of a certain transcription factor or phenotypic marker.…”

Section: Cd4+cd28null T Cells Drive Ms Progressionmentioning

confidence: 98%

Cytotoxic CD4+ T Cells Drive Multiple Sclerosis Progression

et al. 2017

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Multiple sclerosis (MS) is the leading cause of chronic neurological disability in young adults. The clinical disease course of MS varies greatly between individuals, with some patients progressing much more rapidly than others, making prognosis almost impossible. We previously discovered that cytotoxic CD4+ T cells (CD4+ CTL), identified by the loss of CD28, are able to migrate to sites of inflammation and that they contribute to tissue damage. Furthermore, in an animal model for MS, we showed that these cells are correlated with inflammation, demyelination, and disability. Therefore, we hypothesize that CD4+ CTL drive progression of MS and have prognostic value. To support this hypothesis, we investigated whether CD4+ CTL are correlated with worse clinical outcome and evaluated the prognostic value of these cells in MS. To this end, the percentage of CD4+CD28null T cells was measured in the blood of 176 patients with relapsing-remitting MS (=baseline). Multimodal evoked potentials (EP) combining information on motoric, visual, and somatosensoric EP, as well as Kurtzke expanded disability status scale (EDSS) were used as outcome measurements at baseline and after 3 and 5 years. The baseline CD4+CD28null T cell percentage is associated with EP (P = 0.003, R2 = 0.28), indicating a link between these cells and disease severity. In addition, the baseline CD4+CD28null T cell percentage has a prognostic value since it is associated with EP after 3 years (P = 0.005, R2 = 0.29) and with EP and EDSS after 5 years (P = 0.008, R2 = 0.42 and P = 0.003, R2 = 0.27). To the best of our knowledge, this study provides the first direct link between the presence of CD4+ CTL and MS disease severity, as well as its prognostic value. Therefore, we further elaborate on two important research perspectives: 1° investigating strategies to block or reverse pathways in the formation of these cells resulting in new treatments that slow down MS disease progression, 2° including immunophenotyping in prediction modeling studies to aim for personalized medicine.

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“…The STAT5-mediated IL-2 signaling pathway, a potent inhibitor of the Bcl-6 transcriptional factor and follicular T helper cell differentiation [ 91 ], promotes the expression of T-bet transcriptional factor in CD4 + T cells [ 75 ]. At this respect, it has been shown that Th1 EM cells have sustained expression of T-bet, both in humans [ 92 ] and mice [ 75 ]. T-bet upregulates IFN- γ production but is also an important target of IFN- γ signaling [ 93 ].…”

Section: Ifn- γ Priming Effects On mentioning

confidence: 99%

IFN-γPriming Effects on the Maintenance of Effector Memory CD4⁺T Cells and on Phagocyte Function: Evidences from Infectious Diseases

Silva

Fonseca

Álvarez

et al. 2015

Journal of Immunology Research

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Although it has been established that effector memory CD4+ T cells play an important role in the protective immunity against chronic infections, little is known about the exact mechanisms responsible for their functioning and maintenance, as well as their effects on innate immune cells. Here we review recent data on the role of IFN-γ priming as a mechanism affecting both innate immune cells and effector memory CD4+ T cells. Suboptimal concentrations of IFN-γ are seemingly crucial for the optimization of innate immune cell functions (including phagocytosis and destruction of reminiscent pathogens), as well as for the survival and functioning of effector memory CD4+ T cells. Thus, IFN-γ priming can thus be considered an important bridge between innate and adaptive immunity.

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Human Memory, but Not Naive, CD4+ T Cells Expressing Transcription Factor T-bet Might Drive Rapid Cytokine Production

Abstract: Background: Human memory CD4ϩ T cells mediate adaptive immune responses via rapidly producing effector cytokines.

Cited by 20 publications

References 30 publications

Multi-color flow cytometry for evaluating age-related changes in memory lymphocyte subsets in dogs

Multi-color flow cytometry for evaluating age-related changes in memory lymphocyte subsets in dogs

Cytotoxic CD4+ T Cells Drive Multiple Sclerosis Progression

IFN-γPriming Effects on the Maintenance of Effector Memory CD4⁺T Cells and on Phagocyte Function: Evidences from Infectious Diseases

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Human Memory, but Not Naive, CD4+ T Cells Expressing Transcription Factor T-bet Might Drive Rapid Cytokine Production

Abstract: Background: Human memory CD4ϩ T cells mediate adaptive immune responses via rapidly producing effector cytokines.

Cited by 20 publications

References 30 publications

Multi-color flow cytometry for evaluating age-related changes in memory lymphocyte subsets in dogs

Multi-color flow cytometry for evaluating age-related changes in memory lymphocyte subsets in dogs

Cytotoxic CD4+ T Cells Drive Multiple Sclerosis Progression

IFN-γPriming Effects on the Maintenance of Effector Memory CD4+T Cells and on Phagocyte Function: Evidences from Infectious Diseases

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Product

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IFN-γPriming Effects on the Maintenance of Effector Memory CD4⁺T Cells and on Phagocyte Function: Evidences from Infectious Diseases