HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS.
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.
Nilsson
Jakob
J
Division of Molecular Immunology (ML#7021), Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA.
Boasso
Adriano
A
Velilla
Paula Andrea
PA
Zhang
Rui
R
Vaccari
Monica
M
Franchini
Genoveffa
G
Shearer
Gene M
GM
Andersson
Jan
J
Chougnet
Claire
C
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D000328:Adult; D000943:Antigens, Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014779:Virus Replication / Q000276:immunology*
D000943:Antigens, Differentiation; D015699:HIV Envelope Protein gp120