T cells and viral persistence: lessons from diverse infections

Klenerman, Paul; Hill, Ann B.

doi:10.1038/ni1241

Cited by 376 publications

(320 citation statements)

References 96 publications

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“…This change is partially due to thymic involution and reductions in hematopoietic stem cells committed to lymphoid lineage development, but also results from large expansions of CMV-specific T cells observed in older people, creating the paradigm of CMV-induced T cell Bmemory inflation^ (Khan et al 2002;Klenerman and Hill 2005;Whiting et al 2015). Of interest, in the absence of CMV infection, aging alone does not result in increased absolute numbers of memory T cells in the blood (Wertheimer et al 2014).…”

Section: Immune Aging and CMVmentioning

confidence: 99%

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

Souquette¹,

Frere²,

Smithey³

et al. 2017

GeroScience

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Approximately 50% of individuals aged 6-49 years in the United States are infected with cytomegalovirus (CMV), with seroprevalence increasing with age, reaching 85-90% by 75-80 years according to Bate et al. (Clin Infect Dis 50 (11): 1439-1447 and Pawelec et al. (Curr Opin Immunol 24:507-511, 2012). Following primary infection, CMV establishes lifelong latency with periodic reactivation. Immunocompetent hosts experience largely asymptomatic infection, but CMV can cause serious illness in immunocompromised populations, such as transplant patients and the elderly. Control of CMV requires constant immune surveillance, and recent discoveries suggest this demand alters general features of the immune system in infected individuals. Here, we review recent advances in the understanding of the immune response to CMV and the role of CMV in immune aging and fitness, while highlighting the importance of potential confounding factors that influence CMV studies. Understanding how CMV contributes to shaping Bbaseline^immunity has important implications for a host's ability to mount effective responses to diverse infections and vaccination.

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Section: Immune Aging and CMVmentioning

confidence: 99%

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

Souquette¹,

Frere²,

Smithey³

et al. 2017

GeroScience

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“…A different outcome arises when infections become chronic and when viruses persist at high levels over long periods as in Human-Immunodeficiency-Virus (HIV) or Human-Hepatitis-C Virus (HCV) infections. Such conditions induce T-cells lacking the typical polyfunctional phenotype and T-cells retain the expression of inhibitory receptors including PD-1, Lag-3, Tim-3, and CD160 [9][10][11][12][13][14][15][16][17] . Very similar phenotypes can be observed, when T-cells are long-term exposed to tumor-antigen [18][19][20] .…”

Section: Introductionmentioning

confidence: 99%

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

et al. 2014

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Chronic viral infections and malignant tumours induce T cells that have a reduced ability to secrete effector cytokines and have upregulated expression of the inhibitory receptor PD1 (programmed cell death protein 1). These features have so far been considered to mark terminally differentiated 'exhausted' T cells. However, several recent clinical and experimental observations indicate that phenotypically exhausted T cells can still mediate a crucial level of pathogen or tumour control. In this Opinion article, we propose that the exhausted phenotype results from a differentiation process in which T cells stably adjust their effector capacity to the needs of chronic infection. We argue that this phenotype is optimized to cause minimal tissue damage while still mediating a critical level of pathogen control. In contrast to the presently held view of functional exhaustion, this new concept better reflects the pathophysiology and clinical manifestations of persisting infections, and it provides a rationale for emerging therapies that enhance T cell activity in chronic infection and cancer by blocking inhibitory receptors. Daniel T. Utzschneider Division of Immunology and Allergy of the Lausanne University Hospital (CHUV) and Swiss Vaccine Research Institute (SVRI), Lausanne, SwitzerlandDaniel Utzschneider is a PhD student of Dietmar Zehn. His research is focused on T-cell differentiation in chronic infection. Susanne G. Oberle Division of Immunology and Allergy of the Lausanne University Hospital (CHUV) and Swiss Vaccine Research Institute (SVRI), Lausanne, SwitzerlandSusanne Oberle is a PhD student of Dietmar Zehn. Her research interests are focused on investigating T-cell responses in acute and chronic infections. and it provides a rational for emerging therapies that enhance T-cell activity in chronic infection and cancer by blocking inhibitory receptors. Christian Münz PhD

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“…Cytokine secretion can be limited by the T cell exhaustion state 12, 32 during chronic viral infections 33, 34, malignant tumors 35, and parasitic diseases 36. Chronic chagasic patients displayed dysfunctional T cell responses characterized by increased frequency of terminally differentiated cells, monofunctional antigen‐specific T cell responses and progressive attenuation of cytokine production 7, 10, 21, 37.…”

Section: Discussionmentioning

confidence: 99%

T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

Ripoll

Giraldo

Bolaños

et al. 2017

Immunity Inflam & Disease

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IntroductionChagas disease is a parasitic infection whose pathogenesis is related to parasite persistence and a dysfunctional cellular immune response. Variability in cytokine secretion among chronic Trypanosoma cruzi‐infected patients might preclude the identification of the pool of antigen specific T cells. The goal of this study was to determine the fraction of T cells responding to T. cruzi antigen measured by the expression of membrane TNF‐α and CD154.MethodsA total of 21 chagasic patients, 11 healthy and 5 non‐chagasic cardiomyopathy controls were analyzed. PBMCs were short‐term cultured in the presence of anti‐CD28, anti‐CD49d, anti‐TNF‐α, and TACE (TNF‐α converting enzyme) inhibitor either under T. cruzi‐lysate or polyclonal stimuli. Cells were stained with anti‐CD3, anti‐CD4, anti‐CD8, and anti‐CD154, and analyzed with flow cytometry.ResultsCD4+ and CD8+ T cells in chagasic patients displayed higher percentages of membrane‐bound TNF‐α+ and CD154+ compared with controls after T. cruzi‐antigen stimulation. Both markers displayed a positive correlation in the T cell subpopulations analyzed. Symptomatic chagasic patients were differentiated from asymptomatic patients based on the expression of CD154 and membrane TNF‐α in TCD4+ and TCD8+ compartments, respectively.ConclusionsThese results show that both markers could be useful for assessing the pool of antigen‐specific T cells in chronic chagasic patients.

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T cells and viral persistence: lessons from diverse infections

Cited by 376 publications

References 96 publications

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

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