title: Decreases in IL-7 levels during antiretroviral treatment of HIV infection suggest a primary mechanism of receptor-mediated clearance.
abstract: IL-7 is essential for T-cell homeostasis. Elevated serum IL-7 levels in lymphopenic states, including HIV infection, are thought to be due to increased production by homeostatic feedback, decreased receptor-mediated clearance, or both. The goal of this study was to understand how immune reconstitution through antiretroviral therapy (ART) in HIV(+) patients affects IL-7 serum levels, expression of the IL-7 receptor (CD127), and T-cell cycling. Immunophenotypic analysis of T cells from 29 HIV(-) controls and 43 untreated HIV(+) patients (30 of whom were followed longitudinally for ≤ 24 months on ART) was performed. Restoration of both CD4(+) and CD8(+) T cells was driven by increases in CD127(+) naive and central memory T cells. CD4(+) T-cell subsets were not fully restored after 2 years of ART, whereas serum IL-7 levels normalized by 1 year of ART. Mathematical modeling indicated that changes in serum IL-7 levels could be accounted for by changes in the receptor concentration. These data suggest that T-cell restoration after ART in HIV infection is driven predominantly by CD127(+) cells and that decreases of serum IL-7 can be largely explained by improved CD127-mediated clearance.
authors.affiliation: Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Hodge
authors.forename: Sharat
authors.initials: S
authors.lastname: Srinivasula
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Hu
authors.forename: Sarah W
authors.initials: SW
authors.lastname: Read
authors.forename: Brian O
authors.initials: BO
authors.lastname: Porter
authors.forename: Insook
authors.initials: I
authors.lastname: Kim
authors.forename: Joann M
authors.initials: JM
authors.lastname: Mican
authors.forename: Chang
authors.initials: C
authors.lastname: Paik
authors.forename: Paula
authors.initials: P
authors.lastname: Degrange
authors.forename: Michele
authors.initials: M
authors.lastname: Di Mascio
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000097:blood* / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents; D015851:Interleukin-7; D020395:Receptors, Interleukin-7