title: Altered phenotype of regulatory T cells associated with lack of human immunodeficiency virus (HIV)-1-specific suppressive function.
abstract: Mechanisms by which CD4+ regulatory T cells (T(regs)) mediate suppression of virus-specific responses remain poorly defined. Adenosine, mediated via CD39 and CD73, has been shown to play a role in the action of murine T(regs) . In this study we investigate the phenotype of T(regs) in the context of human immunodeficiency virus (HIV)-1 infection, and the function of these cells in response to HIV-1-Gag and cytomegalovirus (CMV) peptides. Phenotypic data demonstrate a decrease in forkhead box transcription factor 3 (FoxP3+) T(reg) numbers in the peripheral blood of HIV-1+ individuals compared to healthy controls, which is most pronounced in those with high HIV-1 RNA plasma load. Due to aberrant expression of CD27 and CD127 during HIV-1 disease, these markers are unreliable for T(reg) identification. The CD3+ CD4+ CD25(hi) CD45RO+ phenotype correlated well with FoxP3 expression in both the HIV-1+ and seronegative control cohorts. We observed expression of CD39 but not CD73 on T(regs) from HIV-1+ and healthy control cohorts. We demonstrate, through T(reg) depletion, the suppressive potential of T(regs) over anti-CMV responses in the context of HIV-1 infection; however, no recovery of the HIV-1-specific T cell response was observed indicating a preferential loss of HIV-1-specific T(reg) function. We propose that before immunotherapeutic manipulation of T(regs) is considered, the immunoregulatory profile and distribution kinetics of this population in chronic HIV-1 infection must be elucidated fully.
authors: Department of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
authors: C T
authors: CT
authors: Burton
authors: S J
authors: SJ
authors: Westrop
authors: I
authors: I
authors: Eccles-James
authors: A
authors: A
authors: Boasso
authors: M R
authors: MR
authors: Nelson
authors: M
authors: M
authors: Bower
authors: N
authors: N
authors: Imami
mesh_terms: D000241:Adenosine / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis; D018655:Lymphocyte Count; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load; D014764:Viral Proteins / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015851:Interleukin-7; D012367:RNA, Viral; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D000241:Adenosine