Cytomegalovirus infection and progressive differentiation of effector-memory T cells

Pardieck, Iris N.; Beyrend, Guillaume; Redeker, Anke; Arens, Ramon

doi:10.12688/f1000research.15753.1

Cited by 19 publications

(16 citation statements)

References 65 publications

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“…And this is accompanied by an increase of HCMV-specific cells that re-express CD45RA [11] and express KLRG1 [47]. Moreover, using new computational tools, it was recently shown that inflationary MCMV-specific T cells are progressively differentiating in time (based on the markers KLRG1, CD44, CD27 and CD62L), long after the initial infection [74, 85]. In line with these studies is the observation that telomeres of HCMV-specific CD8 T cells are significantly shorter compared to the corresponding phenotypic subsets of the total CD8 T-cell pool [86].…”

Section: Establishment Of the Advanced Differentiation Phenotypementioning

confidence: 99%

The hallmarks of CMV-specific CD8 T-cell differentiation

Berg

Pardieck

Lanfermeijer

et al. 2019

Med Microbiol Immunol

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Upon cytomegalovirus (CMV) infection, large T-cell responses are elicited that remain high or even increase over time, a phenomenon named memory T-cell inflation. Besides, the maintained robust T-cell response, CMV-specific T cells seem to have a distinctive phenotype, characterized by an advanced differentiation state. Here, we will review this "special" differentiation status by discussing the cellular phenotype based on the expression of CD45 isoforms, costimulatory, inhibitory and natural killer receptors, adhesion and lymphocyte homing molecules, transcription factors, cytokines and cytotoxic molecules. In addition, we focus on whether the differentiation state of CMV-specific CD8 T cells is unique in comparison with other chronic viruses and we will discuss the possible impact of factors such as antigen exposure and aging on the advanced differentiation status of CMV-specific CD8 T cells.

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Section: Establishment Of the Advanced Differentiation Phenotypementioning

confidence: 99%

The hallmarks of CMV-specific CD8 T-cell differentiation

Berg

Pardieck

Lanfermeijer

et al. 2019

Med Microbiol Immunol

Self Cite

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“…But this population is on average significantly larger in CKD patients and may comprise over 50% of all circulating CD4 T cells [47]. Remarkably not all CMV seropositive individuals have such an expansion of CD4CD28 negative T cells, which is likely related to the initial infectious dose and the number of CMV reactivations [51,[59][60][61][62]. The total number of CD8 T cells is less affected by ageing, as the decline in naïve CD8 T cells is compensated by an expansion of highly differentiated memory T cells.…”

Section: Renal Failure and Adaptive Immunitymentioning

confidence: 99%

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Betjes

2020

Toxins

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Progressive loss of renal function is associated with a series of changes of the adaptive immune system which collectively constitute premature immunological ageing. This phenomenon contributes significantly to the mortality and morbidity of end-stage renal disease (ESRD) patients. In this review, the effect of ESRD on the T cell part of the adaptive immune system is highlighted. Naïve T cell lymphopenia, in combination with the expansion of highly differentiated memory T cells, are the hallmarks of immunological ageing. The decreased production of newly formed T cells by the thymus is critically involved. This affects both the CD4 and CD8 T cell compartment and may contribute to the expansion of memory T cells. The expanding populations of memory T cells have a pro-inflammatory phenotype, add to low-grade inflammation already present in ESRD patients and destabilize atherosclerotic plaques. The effect of loss of renal function on the thymus is not reversed after restoring renal function by kidney transplantation and constitutes a long-term mortality risk factor. Promising results from animal experiments have shown that rejuvenation of the thymus is a possibility, although not yet applicable in humans.

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“…As previously described, MCMV replication in most organs is initially controlled in the course of the first week while specific T cell are primed. After antigen clearance, virus-specific memory Vaccines 2019, 7, 152 9 of 28 T cells are preserved and, in contrast to naïve T cells, rapidly respond upon re-encounter with a cognate antigen through direct effector functions or further proliferation and differentiation into a more advanced phenotype [115]. Memory subsets have been categorized, according to their functions, location, migration abilities and maintenance requirements into central memory T cells (TCM), effector memory T cells (TEM), tissue-resident memory T cells (TRM) and peripheral memory cells (TPM) [116].…”

Section: Cellular Response-t Cellsmentioning

confidence: 99%

“…Besides the well-described typical pattern of expansion and contraction of antigen-specific T cells, CMV infection is characterized by memory inflation [8], a virus-specific T cell response with skewed specificity that continues to expand during viral persistence [9,117]. This "inflationary" population is represented by circulating TEM (CD62L − ) which in contrast to TCM (CD62L + ) have a phenotype compatible with recent antigen activation that is believed to be induced by low level viral persistence through sporadic reactivation events [96,115]. Unlike other persistent infections such as HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV), CMV infection leads to the production of fully functional, virus-specific T cells without any hallmarks of immune exhaustion [118,119].…”

Section: Cellular Response-t Cellsmentioning

confidence: 99%

Vaccine Vectors Harnessing the Power of Cytomegaloviruses

2019

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Cytomegalovirus (CMV) species have been gaining attention as experimental vaccine vectors inducing cellular immune responses of unparalleled strength and protection. This review outline the strengths and the restrictions of CMV-based vectors, in light of the known aspects of CMV infection, pathogenicity and immunity. We discuss aspects to be considered when optimizing CMV based vaccines, including the innate immune response, the adaptive humoral immunity and the T-cell responses. We also discuss the antigenic epitopes presented by unconventional major histocompatibility complex (MHC) molecules in some CMV delivery systems and considerations about routes for delivery for the induction of systemic or mucosal immune responses. With the first clinical trials initiating, CMV-based vaccine vectors are entering a mature phase of development. This impetus needs to be maintained by scientific advances that feed the progress of this technological platform.Vaccines 2019, 7, 152 2 of 28 CMV-based vaccines, the large pool of functional antigen-specific T cells in the periphery and the possibility to modify CMV genomes due to improvements in viral genetics [11] draw a strong interest to CMV as a vaccine vector [12,13] (Table 1). The inflationary response appears linked to immune protection [14,15] and has been proposed as a target for immunization induction [16]. Vaccines 2019, 7, 152 3 of 28 Full-length HPV16 E6 and E7 Antigen fused to the C-terminus of ie2 Transient limitation of tumour cell growth MCMV IE2E7 [14] MHC-I restricted HPV16 E7 49-57 epitope Epitope fused to the C-terminus of ie2 No tumour cell growth upon challenge MCMV-M79-FKBP-E7 [36] MCMV Smith Strain with FKBP-mediated destabilization of the essential M79 gene Vaccines 2019, 7, 152 5 of 28Besides the exceptional induction of adaptive immune response in humans [2,37], CMV possesses assets that conveniently address weaknesses common to other vector candidates. The cloning of CMV genomes as bacterial artificial chromosomes in Escherichia coli [38] has allowed genetic engineering approaches to effectively express multiple exogenous immunogens or modify large genome portions [39,40]. Furthermore, CMV is known to superinfect hosts with a history of prior exposure to the virus [41] due to its immune evasive properties that protect the virus from recognition by primed T-cells [42] and CMV vectors induce protective immunity in experimentally vaccinated animals with documented prior exposure to 36]. Therefore, CMV vector candidates would avoid immune interference as described for AdV. CMV is a pathogenic organism in immunodeficient populations [43] or in congenitally infected children. Therefore, it is imperative for any HCMV vaccine vector to be attenuated. The generation of replication deficient CMVs that maintain their immunogenicity [36,44] and the modification of genome portions that contain evasions genes [45], as well as the insertion of activating ligands to increase immune control of CMV [46][47][48] are strategies that will be described in this review. Inter...

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Cytomegalovirus infection and progressive differentiation of effector-memory T cells

Cited by 19 publications

References 65 publications

The hallmarks of CMV-specific CD8 T-cell differentiation

The hallmarks of CMV-specific CD8 T-cell differentiation

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Vaccine Vectors Harnessing the Power of Cytomegaloviruses

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