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Higher Body Mass Index Is Associated With Greater Proportions of Effector CD8+ T Cells Expressing CD57 in Women Living With HIV
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"our findings suggest that some degree of adiposity may counteract the adverse changes in T-cell differentiation seen in untreated HIV infection.” in HIV+ Women with high BMI & circumference - WIHS
We speculate that this difference may be more consistent with a decreased immune activation (associated with a reduced catabolic state and greater BMI) in HIV allowing for greater terminal differentiation of effector CD8+ T cells, in contrast to a scenario where increased immune activation in obese adolescents drives CD28-CD8+ T cells to express CD57. Nevertheless, we cannot exclude the possibility that the association between BMI and terminally differentiated CD8+ T cells are associated with long-term deleterious health effects.
In conclusion, in a relatively large cohort of HIV-infected women on ART, we found that greater BMI is associated with greater expression of CD57 on the proportion of CD28-CD8+ T cells, and increase in the proportion of CD57+CD28-CD8+ T cells, but not an accumulation of the overall CD28-CD8+ T-cell subset. The impact of body composition on CD8+ T-cell phenotype is complex in the setting of HIV infection, given known effects of HIV on lean mass and subcutaneous tissue. Future research is needed using careful assessment of the various body composition compartments to understand the prognostic importance of these associations on clinical outcomes in HIV-infected individuals.
Higher Body Mass Index Is Associated With Greater Proportions of Effector CD8+ T Cells Expressing CD57 in Women Living With HIV
JAIDS Aug 15 2017 - Reid, Michael J. A. MD, MPH*; Baxi, Sanjiv M. MD, PhD, MPH; Sheira, Lila A. MPH; Landay, Alan L. PhD§; Frongillo, Edward A. PhD‖; Adedimeji, Adebola PhD; Cohen, Mardge H. MD; Wentz, Eryka MA**; Gustafson, Deborah R. PhD; Merenstein, Daniel MD; Hunt, Peter W. MD*,; Tien, Phyllis C. MD*,§§; Weiser, Sheri D. MD, MA, MPH*,; for the Women's Interagency HIV Study (WIHS)
Background: A low proportion of CD28-CD8+ T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing body mass index (BMI) changes in the proportion of CD57+CD28-CD8+ T cells among HIV-infected individuals on antiretroviral therapy is unknown.
Setting: In a US cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8+ T cell phenotypes: % CD28-CD57+CD8+ T cells, % CD57+ of CD28-CD8+ T cells, and % CD28- of all CD8+ T cells.
Methods: Multivariable linear regression analysis was used to estimate beta coefficients for each of 3 T-cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, and study site), and lifestyle (tobacco and alcohol use) factors.
Results: Of 225 participants, the median age was 46 years and 50% were obese (BMI >30 m2/kg). Greater BMI and waist circumference were both associated with higher % CD28-CD57+CD8+ T cells and % CD57+ of all CD28-CD8+ T cells in multivariable analysis, including adjustment for HIV viral load (all P < 0.05). The association between greater BMI and the overall proportion of CD28- CD8+ cells in fully adjusted models (0.078, 95% confidence interval: -0.053 to 0.209) was not significant.
Conclusions: In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD28-CD8+ T cells and a greater proportion of CD57+CD28- CD8+ T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes.
INTRODUCTION
The advent of highly active antiretroviral therapy (ART) has had a profound impact on HIV-associated morbidity and mortality.1 Although the prevalence of HIV-associated wasting has declined, the proportion of overweight and obese HIV-infected individuals is increasing.2 Although recent studies have failed to show a consistent effect for obesity in the pathogenesis of cardiovascular disease in HIV-infected individuals,3,4 there is evidence demonstrating that obese HIV-infected individuals have a greater prevalence of metabolic diseases, including type 2 diabetes mellitus, compared with nonobese persons.5–7 In addition, increasing body mass index (BMI) is associated with greater innate and adaptive immune activation, even in the setting of treated HIV infection.8,9 As observed in the general population,10 serum levels of systemic markers of inflammation such as C-reactive protein and tumor necrosis factor alpha11–13 are higher among HIV-infected adults with greater adiposity. There is also evidence that adiposity influences adaptive immune responses, with several recent studies suggesting that obesity independently influences immunologic recovery in individuals initiating ART.14–17
Whether increasing BMI also influences the development of other immune defects in HIV-infected individuals is less clear. Studies have demonstrated that HIV infection leads to numerous CD8+ T-cell abnormalities, some of which are also seen in elderly populations (eg, an expansion of CD28- CD8+ T cells) and some of which are distinct from those observed in the elderly (eg, decreased terminal differentiation and a reduced proportion of CD28-CD8+ T cells that express CD57).18,19 It is possible that increasing adiposity may further affect T-cell differentiation because of elevations in systemic low-grade inflammation, heightened oxidative stress,20 alterations in nutrition and micronutrients,21,22 psychosocial factors such as depression and poor quality of life,23 or perturbations in serum concentrations of leptin, which has been shown to influence T-cell activation and proliferation.24
The aim of our study was to investigate the relationship between BMI and CD8+ T-cell phenotypes that have been previously linked to mortality in a diverse cohort of HIV-infected women, while adjusting for potential confounders such as socioeconomic factors, lifestyle and behavioral variables, and HIV viral load. Given the numerous deleterious inflammatory and metabolic sequelae of obesity,9,11 we hypothesized that greater BMI would be associated with a pattern of poor CD8+ T-cell differentiation in HIV-infected adults that has been previously associated with mortality in this setting.
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