Origin and fine-tuning of effector CD8 T cell subpopulations in chronic infection

Kanev, Kristiyan; Zehn, Dietmar

doi:10.1016/j.coviro.2020.10.003

Cited by 5 publications

(6 citation statements)

References 87 publications

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“…Because cytotoxic CD8 T cells are predominantly involved in the killing of virus infected cells and CD4 T cell help is required for CD8 T cell priming, maintenance of CD8 T cell memory and prevention of exhaustion (100,101), it is likely that both class Iand class II-restricted antigen presentation is involved in EBV control. An interaction between EBV infection and HLA genes associated with MS risk is suggested by the finding that HLA-DRB1*15 carriers with higher anti-EBNA-1 antibody titers have a markedly elevated risk of MS (102)(103)(104), which is increased further in the absence of the protective allele HLA-A*0201 (103).…”

Section: Ebv Immunologymentioning

confidence: 99%

The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis

Veroni

Aloisi

2021

Front. Immunol.

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The cause and the pathogenic mechanisms leading to multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), are still under scrutiny. During the last decade, awareness has increased that multiple genetic and environmental factors act in concert to modulate MS risk. Likewise, the landscape of cells of the adaptive immune system that are believed to play a role in MS immunopathogenesis has expanded by including not only CD4 T helper cells but also cytotoxic CD8 T cells and B cells. Once the key cellular players are identified, the main challenge is to define precisely how they act and interact to induce neuroinflammation and the neurodegenerative cascade in MS. CD8 T cells have been implicated in MS pathogenesis since the 80’s when it was shown that CD8 T cells predominate in MS brain lesions. Interest in the role of CD8 T cells in MS was revived in 2000 and the years thereafter by studies showing that CNS-recruited CD8 T cells are clonally expanded and have a memory effector phenotype indicating in situ antigen-driven reactivation. The association of certain MHC class I alleles with MS genetic risk implicates CD8 T cells in disease pathogenesis. Moreover, experimental studies have highlighted the detrimental effects of CD8 T cell activation on neural cells. While the antigens responsible for T cell recruitment and activation in the CNS remain elusive, the high efficacy of B-cell depleting drugs in MS and a growing number of studies implicate B cells and Epstein-Barr virus (EBV), a B-lymphotropic herpesvirus that is strongly associated with MS, in the activation of pathogenic T cells. This article reviews the results of human studies that have contributed to elucidate the role of CD8 T cells in MS immunopathogenesis, and discusses them in light of current understanding of autoreactivity, B-cell and EBV involvement in MS, and mechanism of action of different MS treatments. Based on the available evidences, an immunopathological model of MS is proposed that entails a persistent EBV infection of CNS-infiltrating B cells as the target of a dysregulated cytotoxic CD8 T cell response causing CNS tissue damage.

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Section: Ebv Immunologymentioning

confidence: 99%

The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis

Veroni

Aloisi

2021

Front. Immunol.

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“…Similarly, prolonged stimulation by antigens in the infected microenvironment also leads to the exhaustion of CD8 T cells. 139 Typically, T cell exhaustion is associated with multiple changes such as impaired proliferative capacity, decreased cytokine production, unique epigenetic modifications, and persistently high expression of multiple inhibitory receptors (PD-1, TIM-3, LAG-3, CTLA-4, and TIGIT). 140 Therefore, to rapidly restore normal T cell function and reduce the risk of disease recurrence, current oncology strategies include biomaterial-directed delivery of immune checkpoint inhibitors and adoptive T cell therapies.…”

Section: Modulation Of Infection Microenvironment Using Immunomodulat...mentioning

confidence: 99%

Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives

Zhang,

Yang,

Wang

et al. 2023

The Innovation

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“…In chronic viral infection, constant expression of viral antigens often leads to the loss of T cell functions, a phenomenon well known as T cell exhaustion (Kanev and Zehn, 2021). How T cells interact with persistent pathogens like gammaherpesviruses is determined by the amount of T cell exhaustion as a hallmark of chronic infections (Saeidi et al, 2018).…”

Section: Gammaherpesvirus Control By T Cells: Role Of T Cell Activati...mentioning

confidence: 99%

The innate and T-cell mediated immune response during acute and chronic gammaherpesvirus infection

Rex

Zargari

Stempel

et al. 2023

Front. Cell. Infect. Microbiol.

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Immediately after entry into host cells, viruses are sensed by the innate immune system, leading to the activation of innate antiviral effector mechanisms including the type I interferon (IFN) response and natural killer (NK) cells. This innate immune response helps to shape an effective adaptive T cell immune response mediated by cytotoxic T cells and CD4+ T helper cells and is also critical for the maintenance of protective T cells during chronic infection. The human gammaherpesvirus Epstein-Barr virus (EBV) is a highly prevalent lymphotropic oncovirus that establishes chronic lifelong infections in the vast majority of the adult population. Although acute EBV infection is controlled in an immunocompetent host, chronic EBV infection can lead to severe complications in immunosuppressed patients. Given that EBV is strictly host-specific, its murine homolog murid herpesvirus 4 or MHV68 is a widely used model to obtain in vivo insights into the interaction between gammaherpesviruses and their host. Despite the fact that EBV and MHV68 have developed strategies to evade the innate and adaptive immune response, innate antiviral effector mechanisms still play a vital role in not only controlling the acute infection but also shaping an efficient long-lasting adaptive immune response. Here, we summarize the current knowledge about the innate immune response mediated by the type I IFN system and NK cells, and the adaptive T cell-mediated response during EBV and MHV68 infection. Investigating the fine-tuned interplay between the innate immune and T cell response will provide valuable insights which may be exploited to design better therapeutic strategies to vanquish chronic herpesviral infection.

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Origin and fine-tuning of effector CD8 T cell subpopulations in chronic infection

Cited by 5 publications

References 87 publications

The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis

The CD8 T Cell-Epstein-Barr Virus-B Cell Trialogue: A Central Issue in Multiple Sclerosis Pathogenesis

Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives

The innate and T-cell mediated immune response during acute and chronic gammaherpesvirus infection

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