Skip Navigation LinksHome > May 1, 2014 - Volume 66 - Issue 1 > Regulatory T Cells and the Risk of CMV End-Organ Disease in...
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‡‡

Supplemental Author Material
Collapse Box

Abstract

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

Login

Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.