Peroxiredoxin II Regulates Effector and Secondary Memory CD8<sup>+</sup>T Cell Responses

Michalek, Ryan D.; Crump, Katie E.; Weant, Ashley E.; Hiltbold, Elizabeth M.; Juneau, Daniel; Moon, Eun‐Yi; Yu, Dae‐Yeul; Poole, Leslie B.; Grayson, Jason M.

doi:10.1128/jvi.01559-12

Cited by 12 publications

(16 citation statements)

References 52 publications

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“…For example, there are reports showing that a small number of lymphocytes (1-10%) can be damaged by exercise and become apoptotic [23] . It is unlikely that this small number of apoptotic cells could account for the changes in levels of PRDX-2 in total lymphocytes directly, but PRDX-2 may be down-regulated in undamaged lymphocytes [8,9] . Such PRDX-2 down-regulation, which is implicated in lymphocyte proliferation, might function to replace "senescent" cells, such as terminally differentiated virus-specific T lymphocytes, which are characteristic of an ageing adaptive immune system [24] .…”

Section: Discussionmentioning

confidence: 99%

“…Twentyfour hours after exercise the level of PRDX-2 had fallen to 74% of pre-race values (t (8) = 0.854, p = 0.418). Seven-days after exercise PRDX-2 level fell to 30% of prerace values (paired samples t-test; t (8) 3.187, p = 0.013). Twenty eight days postrace PRDX-2 returned to a similar level to that measured twenty-four hours after the race, which was not significantly different from baseline (76% of pre-race values; paired samples t-test; t (8) 1.037, p = 0.330).…”

Section: Lymphocyte and Monocyte Numbers Before And After Ultra-endurmentioning

confidence: 93%

“…Moreover, low intracellular antioxidant levels and redox-sensitivity have been implicated in the reactivation of latent viruses [6] and there is substantial evidence that large volumes of exercise are associated with periods of illness [7] . Conversely, very low levels of PRDX-2 are associated with uncontrolled immune activation that might exacerbate inflammatory activity following exercise [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

“…A major role for reduced peroxiredoxins is the control of redoxdependent intracellular signaling, and therefore a variety of cell functions by regulating hydrogen peroxide levels [13] . Indeed, PRDX-2 is the most abundant antioxidant enzyme in the cytosol of lymphocytes, and its levels appear to be involved in the regulation of lymphocyte function [8,14] . Conversely, monocytes, a relatively minor proportion of mononuclear cells in blood, contain little or no PRDX-2 [15] .…”

Section: Introductionmentioning

confidence: 99%

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The antioxidant enzyme peroxiredoxin-2 is depleted in lymphocytes seven days after ultra-endurance exercise

Turner

Bennett

Campbell

et al. 2013

Free Radical Research

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Lymphocyte PRDX-2 was decreased below normal levels 7 days after ultra-endurance exercise. Excessive accumulation of reactive oxygen species induced by ultra-endurance exercise may underlie depletion of lymphocyte PRDX-2 by triggering its turnover after oxidation. Low levels of lymphocyte PRDX-2 could influence cell function and might, in part, explain reports of dysregulated immunity following ultra-endurance exercise.

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Section: Discussionmentioning

confidence: 99%

Section: Lymphocyte and Monocyte Numbers Before And After Ultra-endurmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The antioxidant enzyme peroxiredoxin-2 is depleted in lymphocytes seven days after ultra-endurance exercise

Turner

Bennett

Campbell

et al. 2013

Free Radical Research

View full text Add to dashboard Cite

show abstract

“…, and K b ORF61-524-531 major histocompatibility complex (MHC) class I tetramers were generated as previously described (32). Surface staining was performed by incubation of Abs at a 1:100 dilution in fluorescence-activated cell sorter (FACS) buffer for 30 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Gammaherpesvirus Latency Differentially Impacts the Generation of Primary versus Secondary Memory CD8⁺T Cells during Subsequent Infection

Barton

Rajkarnikar

Langston

et al. 2014

J Virol

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Unlike laboratory animals, humans are infected with multiple pathogens, including the highly prevalent herpesviruses. The purpose of these studies was to determine the effect of gammaherpesvirus latency on T cell number and differentiation during subsequent heterologous viral infections. Mice were first infected with murine gammaherpesvirus 68 (MHV68), a model of EpsteinBarr virus (EBV) infection, and then after latency was established, they were challenged with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV). The initial replication of LCMV was lower in latently infected mice, and the maturation of dendritic cells was abated. Although the number of LCMV-specific effector CD8؉ T cells was not altered, they were skewed to a memory phenotype. In contrast, LCMV-specific effector CD4؉ T cells were increased in latently infected mice compared to those in mice infected solely with LCMV. When the memory phase was reached, latently infected mice had an LCMVspecific memory T cell pool that was increased relative to that found in singly infected mice. Importantly, LCMV-specific memory CD8؉ T cells had decreased CD27 and increased killer cell lectin-like receptor G1 (KLRG1) expression. Upon secondary challenge, LCMV-specific secondary effector CD8 ؉ T cells expanded and cleared the infection. However, the LCMV-specific secondary memory CD8 ؉ T cell pool was decreased in latently infected animals, abrogating the boosting effect normally observed following rechallenge. Taken together, these results demonstrate that ongoing gammaherpesvirus latency affects the number and phenotype of primary versus secondary memory CD8 ؉ T cells during acute infection. IMPORTANCE CD8 ؉ T cells are critical for the clearance of intracellular pathogens, including viruses, certain bacteria, and tumors. However, current models for memory CD8؉ T cell differentiation are derived from pathogen-free laboratory mice challenged with a single pathogen or vaccine vector. Unlike laboratory animals, all humans are infected with multiple acute and chronic pathogens, including the highly prevalent herpesviruses Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex viruses (HSV), and varicella-zoster virus (VZV). The purpose of these studies was to determine the effect of gammaherpesvirus latency on T cell number and differentiation during subsequent heterologous viral infections. We observed that ongoing gammaherpesvirus latency affects the number and phenotype of primary versus secondary memory CD8 ؉ T cells during acute infection. These results suggest that unlike pathogen-free laboratory mice, infection or immunization of latently infected humans may result in the generation of T cells with limited potential for long-term protection.

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Treatment with Exogenously Added Catalase Alters CD8 T Cell Memory Differentiation and Function

Aksoylar

Patsoukis

2022

Advanced Biology

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Cell‐based immunotherapy is a promising approach to cancer treatment. However, the metabolically hostile tumor microenvironment (TME) poses a major barrier to this therapeutic approach. Metabolic reprogramming may enhance T cell effector function and support longevity and persistence within the TME. Metabolic processes lead reactive oxygen species (ROS) production, which are mandatory mediators of signaling and immune cell functions, but detrimental when present in excess. Catalase (CAT) is an intracellular antioxidant enzyme that scavenges hydrogen peroxide (H2O2), a central ROS member with a plethora of biological effects. H2O2 is produced intracellularly and extracellularly, diffusing freely between the two compartments. In this study, it is found that scavenging extracellular H2O2 by CAT supplementation has a major impact on the cell redox state, decreased intracellular ROS, but enhanced activation and altered memory differentiation. Under in vitro chronic activation conditions, CAT treatment favors CD8 T cells with less exhausted phenotype, increased activation and memory markers, and high bioenergetic capacity. Under in vitro acute activation conditions, CAT treatment selectively prevents differentiation transition from the stem cell memory/naive (TSCM/TN)‐ to the central memory (TCM)‐like phenotype, while enhancing activation and polyfunctionality. The study highlights the critical role of H2O2 as a “hidden player” in T cell fitness and memory differentiation.

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Peroxiredoxin II Regulates Effector and Secondary Memory CD8⁺T Cell Responses

Abstract: These results demonstrate that PrdxII controls effector CD8؉ T cell expansion, secondary memory generation, and immunopathology.

Cited by 12 publications

References 52 publications

The antioxidant enzyme peroxiredoxin-2 is depleted in lymphocytes seven days after ultra-endurance exercise

The antioxidant enzyme peroxiredoxin-2 is depleted in lymphocytes seven days after ultra-endurance exercise

Gammaherpesvirus Latency Differentially Impacts the Generation of Primary versus Secondary Memory CD8⁺T Cells during Subsequent Infection

Treatment with Exogenously Added Catalase Alters CD8 T Cell Memory Differentiation and Function

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Peroxiredoxin II Regulates Effector and Secondary Memory CD8+T Cell Responses

Abstract: These results demonstrate that PrdxII controls effector CD8؉ T cell expansion, secondary memory generation, and immunopathology.

Cited by 12 publications

References 52 publications

The antioxidant enzyme peroxiredoxin-2 is depleted in lymphocytes seven days after ultra-endurance exercise

The antioxidant enzyme peroxiredoxin-2 is depleted in lymphocytes seven days after ultra-endurance exercise

Gammaherpesvirus Latency Differentially Impacts the Generation of Primary versus Secondary Memory CD8+T Cells during Subsequent Infection

Treatment with Exogenously Added Catalase Alters CD8 T Cell Memory Differentiation and Function

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Peroxiredoxin II Regulates Effector and Secondary Memory CD8⁺T Cell Responses

Gammaherpesvirus Latency Differentially Impacts the Generation of Primary versus Secondary Memory CD8⁺T Cells during Subsequent Infection