Heterogeneity of CD4+ and CD8+ T-cell Responses to Cytomegalovirus in HIV-Infected and HIV-Uninfected Men Who Have Sex With Men

Li, Huifen; Margolick, Joseph B.; Bream, Jay H.; Nilles, Tricia L.; Langan, Susan; Bui, Hanhvy T.; Sylwester, Andrew; Picker, Louis J.; Leng, Sean X.

doi:10.1093/infdis/jiu093

Cited by 29 publications

(37 citation statements)

References 15 publications

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“…36 Furthermore, CMV cell-mediated immune responses to the pp65 peptide pool may underestimate total T cell responses against CMV. 37 Thus, the reason for discordance between cellmediated and humoral responses in our HIV-infected participants cannot be entirely explained and further investigation is needed.…”

Section: Cd38mentioning

confidence: 88%

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Erlandson

Allshouse

Rapaport

et al. 2015

AIDS Research and Human Retroviruses

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Cytomegalovirus (CMV) is associated with poor outcomes, including physical function impairment, in older HIV-uninfected adults. Whether CMV is associated with physical functional impairment in HIV-infected adults is unknown. The primary objective of this study was to determine the relationship between CMV-specific humoral and cell-mediated immune responses with functional impairment in well-controlled HIV infection. In a case-control study, low-function cases were matched by age, gender, and time from HIV diagnosis to highfunction controls. Quantitative CMV IgG and %CMV-specific CD8 + and CD4 + T cells (interferon-c expression following CMV pp65 stimulation) were used to estimate physical function. Among 30 low-function cases and 48 high-function matched controls, CMV IgG ranged from <10 to 8,830 EU/ml, including four controls with results <10 EU/ml. Each log 10 increase in CMV IgG was associated with 5-fold greater odds of low function ( p = 0.01); these findings were robust to adjustment for concomitant CD4 + count, tobacco use, and age; to exclusion of subjects with CMV IgG <10 EU/ml; and to adjustment for hepatitis C viremia. %CMV-specific CD4 + or CD8 + T cells were not associated with low function. In bivariable models, the relationship between CMV IgG and physical function was attenuated and was no longer significant when including IL-6, CD4/CD8 ratio, or the Veterans Aging Cohort Study Index score. High levels of CMV-specific IgG were associated with impaired physical function. Attenuation of the strength of this association in bivariable models suggests an indirect relationship mediated by systemic inflammation and immune suppression.

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Section: Cd38mentioning

confidence: 88%

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Erlandson

Allshouse

Rapaport

et al. 2015

AIDS Research and Human Retroviruses

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“…This virus, which is highly prevalent in both the geriatric population and HIV+ persons, may cause clonal T-cell expansion, leading to immune activation and chronic inflammation with their associated adverse health outcomes (75–79). The potential importance of CMV in the pathogenesis of systemic inflammation is supported by the fact that it is the target for a very large proportion of circulating T cells in both HIV− and HIV+ people, which is often greater than 10% and can be 30–40% (for example,(80)(81;82)).Some studies have found a direct association between positive CMV serology and frailty and functional decline in the elderly (49;83), but data are conflicting (84;85). …”

Section: Chronic CMV Infection Frailty and Hiv Infectionmentioning

confidence: 99%

“…These findings support the hypothesis that chronic CMV infection is correlated with immune activation. Although CMV infection is common in people infected with HIV, and a very large proportion of the T-cell repertoire is devoted to CMV in HIV-infected persons, even those on long term HAART, (39;81;82), it remains to be determined if CMV-induced immune responses are quantitatively related to systemic levels of inflammation or to frailty in either HIV+ or HIV− populations.…”

Section: Chronic CMV Infection Frailty and Hiv Infectionmentioning

confidence: 99%

Understanding Frailty, Aging, and Inflammation in HIV Infection

Leng

Margolick

2015

Curr HIV/AIDS Rep

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Frailty is a clinical syndrome initially characterized in geriatric populations with a hallmark of age-related declines in physiologic reserve and function and increased vulnerability to adverse health outcomes. Recently, frailty has increasingly been recognized as a common and important HIV-associated non-AIDS (HANA) condition. This article provides an overview of our current understanding of frailty and its phenotypic characteristics, and evidence that they are related to aging and to chronic inflammation that is associated with aging and also with long-term treated HIV infection. The etiology of this chronic inflammation is unknown but we discuss evidence linking it to persistent infection with cytomegalovirus in both geriatric populations and people living with HIV infection.

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“…Among HIVinfected and uninfected MSM participants in the MACS, we conducted an extensive study of T cell responses to peptide pools encoded by 19 HCMV ORFs that elicited the largest responses (correlation of 0.9 with total responses) in healthy donors. Our results demonstrate that T cell responses to pp65 and IE1 combined only represented <12% of the total CD4 + and <40% of the total CD8 + T cell responses (Li et al 2014a), suggesting the need for more comprehensive evaluation of the impact of chronic HCMV infection on T cell immunity beyond the commonly tested HCMV pp65 and IE1 epitopes.…”

Section: Chronic CMV Infection In Older Adults: Diagnostic Evaluationmentioning

confidence: 86%

Recent advances in CMV tropism, latency, and diagnosis during aging

et al. 2017

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Human cytomegalovirus (CMV) is one of the largest viruses known to cause human diseases. Chronic CMV infection, as defined by anti-CMV IgG serology, increases with age and is highly prevalent in older adults. It has complex biology with significant immunologic and health consequences. This article aims to summarize research findings presented at the 6th International Workshop on CMV and Immunosenescence that relate to advances in the areas of CMV tropism, latency, CMV manipulation of cell metabolism, and T cell memory inflation, as well as novel diagnostic evaluation and translational research of chronic CMV infection in older adults. Information summarized here represents the current state of knowledge in these important fields. Investigators have also identified a number of areas that deserve further and more in-depth investigation, including building more precise parallels between mouse CMV (mCMV) and human CMV (HCMV) research. It is hoped that this article will also stimulate engaging discussion on strategies and direction to advance the science to the next level.

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Heterogeneity of CD4+ and CD8+ T-cell Responses to Cytomegalovirus in HIV-Infected and HIV-Uninfected Men Who Have Sex With Men

Cited by 29 publications

References 15 publications

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Understanding Frailty, Aging, and Inflammation in HIV Infection

Recent advances in CMV tropism, latency, and diagnosis during aging

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