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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000095
Basic and Translational Science

Regulatory T Cells and the Risk of CMV End-Organ Disease in Patients With AIDS

Weinberg, Adriana MD*; Bosch, Ronald PhD; Bennett, Kara PhD; Tovar-Salazar, Adriana MS*; Benson, Constance A. MD; Collier, Ann C. MD§; Zolopa, Andrew MD; Gulick, Roy M. MD; Wohl, David MD#; Polsky, Bruce MD**; Erice, Alejo MD††; Jacobson, Mark A. MD‡‡

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Objectives: Cytomegalovirus (CMV)-specific T-cell effectors (CMV-Teff) protect against CMV end-organ disease (EOD). In HIV-infected individuals, their numbers and function vary with CD4+ cell numbers and HIV load. The role of regulatory T cells (Treg) in CMV-EOD has not been extensively studied. We investigated the contribution of Treg and Teff toward CMV-EOD in HIV-infected individuals independently of CD4+ cell numbers and HIV load and controlling for CMV reactivations.

Design: We matched 43 CMV-EOD cases to 93 controls without CMV-EOD, but with similar CD4+ cell numbers and HIV plasma RNA. CMV reactivation was investigated by blood DNA polymerase chain reaction over 32 weeks preceding the CMV-EOD in cases and preceding the matching point in controls.

Methods: CMV-Teff and Treg were characterized by the expression of interferon-γ (IFN-γ), interleukin 2, tumor necrosis factor α (TNFα), MIP1β, granzyme B (GrB), CD107a, TNFα, FOXP3, and CD25.

Results: Sixty-five percent cases and 20% controls had CMV reactivations. In multivariate analyses that controlled for CMV reactivations, none of the CMV-Teff subsets correlated with protection, but high CMV-GrB enzyme-linked immunosorbent spot responses and CMV-specific CD4+FOXP3+%, CD4+TNFα+%, and CD8+CD107a+% were significant predictors of CMV-EOD.

Conclusions: Because both FOXP3 and GrB have been previously associated with Treg activity, we conclude that CMV-Treg may play an important role in the development of CMV-EOD in advanced HIV disease. We were not able to identify a CMV-Teff subset that could be used as a surrogate of protection against CMV-EOD in this highly immunocompromised population.

© 2014 by Lippincott Williams & Wilkins


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