Regulatory T cells and the risk of CMV end-organ disease in patients with AIDS.

TitleRegulatory T cells and the risk of CMV end-organ disease in patients with AIDS.
Publication TypeJournal Article
Year of Publication2014
AuthorsWeinberg A, Bosch R, Bennett K, Tovar-Salazar A, Benson CA, Collier AC, Zolopa A, Gulick RM, Wohl D, Polsky B, Erice A, Jacobson MA
JournalJ Acquir Immune Defic Syndr
Volume66
Issue1
Pagination25-32
Date Published2014 May 1
ISSN1944-7884
KeywordsAdult, Case-Control Studies, Cytomegalovirus Infections, Female, HIV Infections, Humans, Leukocytes, Mononuclear, Male, Middle Aged, Risk Assessment, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory
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 CD4FOXP3+%, CD4TNFα+%, and CD8CD107a% 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.

DOI10.1097/QAI.0000000000000095
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID24378728
PubMed Central IDPMC3981937
Grant ListAI 069434 / AI / NIAID NIH HHS / United States
AI 38855 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States
AI 68634 / AI / NIAID NIH HHS / United States
AI 68636 / AI / NIAID NIH HHS / United States
AI-51966 / AI / NIAID NIH HHS / United States
AI-69419 / AI / NIAID NIH HHS / United States
R21 AI073121 / AI / NIAID NIH HHS / United States
R21AI073121 / AI / NIAID NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069419 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States