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PMID: 16902147 Published · ppublish English Clinical Trial Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS.

Blood ·Vol. 108 ·No. 12 ·2006-12-01 ·Pages 3808-17

Nilsson J, Boasso A, Velilla PA, Zhang R, Vaccari M, Franchini G, Shearer GM, Andersson J, Chougnet C

Abstract

Regulatory T (Treg) cells accumulate in the lymphoid tissues of human immunodeficiency virus (HIV)-infected individuals, contributing to the inability of the immune system to control virus replication. We investigate here Treg-cell numbers and functional markers (FOXP3, CTLA-4, IDO, and TGF-beta1) in lymphoid tissues from untreated infected hosts with progressive or nonprogressive disease (HIV-infected humans and simian immunodeficiency virus [SIV]-infected macaques). We found that increased numbers of FOXP3(+) T cells as well as increased expression of Treg-cell-associated functional markers were detected only during progressive disease. Such increases were not correlated with immune activation. Of importance, a high-perforin/FOXP3 ratio was associated with nonprogressive disease, suggesting that the immune control of virus replication represents a balance between cell-mediated immune responses and Treg-cell-mediated counter regulation of such responses. Furthermore, using an in vitro model of Treg-cell-HIV interactions, we showed that exposure of Treg cells to HIV selectively promoted their survival via a CD4-gp120-dependent pathway, thus providing an underlying mechanism for the accumulation of Treg cells in infected hosts with active viral replication. Considered together, our findings imply that therapeutic manipulation of Treg-cell number and/or function could improve immune control of HIV infection.

MeSH Terms
Acquired Immunodeficiency Syndrome/immunology,pathology Adult Antigens, Differentiation/immunology Cell Survival/immunology Cohort Studies Disease Progression Female HIV Envelope Protein gp120/immunology HIV-1/immunology Humans Lymphoid Tissue/immunology,pathology,virology Male Middle Aged Signal Transduction/immunology T-Lymphocytes, Regulatory/immunology,pathology,virology Virus Replication/immunology
Chemicals
Antigens, Differentiation HIV Envelope Protein gp120
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Nilsson Jakob
Division of Molecular Immunology (ML#7021), Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA.
Boasso Adriano
Velilla Paula Andrea
Zhang Rui
Vaccari Monica
Franchini Genoveffa
Shearer Gene M
Andersson Jan
Chougnet Claire
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-05-021576
Published
2006-12-01
Epub
2006-00-10
Pages
3808-17
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895475
Subset
IM
Grants
NIAID NIH HHS · R01 AI068524 · United States
NIAID NIH HHS · AI068524 · United States
External Links
PubMed source DOI: 10.1182/blood-2006-05-021576 PMC Full Text View journal details
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