PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients

Shen, Tao; Zheng, Jiajia; Xu, Chunhui; Liu, Jia; Zhang, Weidong; Lu, Fengmin; Zhang, Hui

doi:10.1186/1743-422x-7-310

Cited by 35 publications

(34 citation statements)

References 51 publications

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“…1A, B). Other immune cell alterations noted were in line with previous studies, including an increase in Tregs [25], a reduced frequency of pDCs [26], and a shift within the CD4 and CD8 T-cell compartments from naïve to antigen-experienced cells [27,28].…”

Section: Mait Cells Are Among the Most Severely Affected Immune Cellssupporting

confidence: 72%

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

et al. 2016

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Additional supporting information may be found in the online version of this article at the publisher's web-site Introduction Mucosal-associated invariant T (MAIT) cells are T cells with innate-like characteristics enriched in human liver and at mucosalCorrespondence: Dr. Niklas K. Björkström e-mail: niklas.bjorkstrom@ki.se sites [1,2]. They express a semi-invariant TCR carrying the Vα7.2 segment together with a restricted Vβ repertoire [1,2]. Upon activation, MAIT cells respond rapidly with cellular cytotoxicity as well as secretion of proinflammatory and anti-viral cytokines such * These authors contributed equally to this work. HCV is an extremely successful pathogen in that it establishes chronic infection in up to 90% of infected humans [9]. The reasons behind the failure of the human immune system to clear HCV are not fully understood but involve viral escape, CD4 and CD8 T-cell exhaustion, as well as NK-cell dysfunction [10][11][12] Until recently, pegylated IFN-α together with ribavirin was used to treat chronic HCV-infection. However, pegylated IFN-α in doses administered to patients has direct inhibitory effects on immune cells [15][16][17][18]. In the last years, treatment of HCV has undergone a revolution with the introduction of highly effective direct-acting antivirals (DAA) that rapidly eliminate the virus [19]. Thus, today the vast majority of patients clear HCV after such IFN-free treatment regimens. This remarkable outcome allows for studies on consequences on immune cell recovery following rapid pathogen removal. In such studies, it was recently shown that both HCVspecific CD8 T cell and NK-cell populations become reinvigorated following viral clearance [20][21][22][23]. However, whether MAIT cells recover upon HCV clearance remains unclear.Here, we performed a comprehensive analysis of MAIT cells in chronic HCV-infection. Specifically, we addressed whether MAIT cell recovery occurs upon HCV-clearance in patients receiving an IFN-free treatment regimen consisting of sofosbuvir and ribavirin. Strikingly, and in contrast to other immune cells, MAIT cells were not reinvigorated following successful HCV-clearance using IFNfree therapy. The results are discussed in relation to the current knowledge on human MAIT cell responses to other viral infections and in the context of immune exhaustion during chronic infections. Results and discussion MAIT cells are among the most severely affected immune cells in chronic HCV-infectionTo determine the impact of chronic HCV-infection on the peripheral blood immune cell compartment, we assessed the major myeloid and lymphoid immune cell subsets in a cohort of HCVpatients and healthy donors by using a 23-parameter flow cytometry staining approach as previously described [24] (Supporting Information Fig. 1). The major phenotype observed in chronic HCV was a severe loss of MAIT cells (Fig. 1A, B). Other immune cell alterations noted were in line with previous studies, including an increase in Tregs [25], a reduced frequency of pDCs [26], and a shift within the CD4...

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Section: Mait Cells Are Among the Most Severely Affected Immune Cellssupporting

confidence: 72%

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

et al. 2016

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“…In addition to the direct effect of HCV, other factors may also enhance MDSC expansion. It is known that infection of hepatocytes by HCV could lead to inflammation in the liver and secretion of inflammatory cytokines, which can result in immune activation in chronic HCV-infected individuals [25,26]. The correlation between MDSCs and activated T cells support that inflammatory status may be an alternative mechanism for MDSC expansion in CHC patients.…”

Section: Discussionmentioning

confidence: 97%

“…In addition to clinical markers of HCV infection, the correlation between MDSC and immunological markers was also evaluated. It is known that exposure of HCV viral antigens results in chronic immune activation that could dampen antigen-specific T cell responses and contribute to immune evasion of HCV [25,26]. The typical readout for this immune activation is detection of CD38 + activated T cells in PBMCs.…”

Section: Elevation Of Mdsc Frequency In the Peripheral Blood Of Chc Pmentioning

confidence: 99%

Clinical Significance and Functional Studies of Myeloid-Derived Suppressor Cells in Chronic Hepatitis C Patients

et al. 2013

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“…EM, effector memory. CM (7,15,16,23) in healthy volunteers as well as in clinical settings including transplantation despite the fact that these cells are lacking CCR7 expression. Indeed, the characteristics of the subsets that were identified using either CD45RA -CCR7 þ or CD45RA -CD27 þ were in sharp contrast.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, there appears to have been an evolution in the subsets identified using CD45RA and CD27. While this nomenclature was pioneered as being able to identify na€ ıve, effector, and memory subsets (14), over time it has begun to be misused as a means to identify na€ ıve, central memory (CM), effector memory (EM), and T cell effector memory re-expressing CD45RA (TEMRA) populations (7,15,16). The aim of the study was to investigate the similarities and differences of the subsets identified by using three nomenclatures (CD45RA and CCR7, CD45RA and CD27, and CD45RA and CD28) in a large cohort of kidney transplant recipients with stable graft function and standard immunosuppressive regimen.…”

Section: Introductionmentioning

confidence: 99%

Benefits of Using CD45RA and CD28 to Investigate CD8 Subsets in Kidney Transplant Recipients

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Tilly

Giral

et al. 2016

American Journal of Transplantation

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The deleterious role of CD8 T cells in kidney graft outcome has regained interest over the years, and memory T cells are considered as one of the main hurdles to achieve transplantation success. Monitoring the CD8 immune response in transplant recipients involved a heterogeneous combination of markers, but the justification of their choice is rarely stated. Whereas the number of parameters is not an issue in phenotypic analysis, functional assays have to accommodate the cell number with the narrowing of the subset. The aim of the study was to investigate the similarities and differences of the subsets identified using three nomenclatures (CD45RA and CCR7/CD27/ CD28) in kidney transplant recipients with stable graft function. We found that all three nomenclatures can identify na€ ıve and effector memory (EM) rheumatoid arthritis T cell CD8 with similar features. Whereas CM CD8 could only be documented using CCR7 and CD45RA, the characteristics of EM CD8 will differ according to the nomenclature. We found that the use of the CD45RA and CD28 gives the benefit of examining two EM populations at early and late differentiation states. This systematic comparison provides a cohesive layout of the advantages of using these nomenclature strategies in kidney transplant recipients to guide the choice of their use.

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PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients

Cited by 35 publications

References 51 publications

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

Nonreversible MAIT cell‐dysfunction in chronic hepatitis C virus infection despite successful interferon‐free therapy

Clinical Significance and Functional Studies of Myeloid-Derived Suppressor Cells in Chronic Hepatitis C Patients

Benefits of Using CD45RA and CD28 to Investigate CD8 Subsets in Kidney Transplant Recipients

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