title: Persistent human immunodeficiency virus-1 antigenaemia affects the expression of interleukin-7Ralpha on central and effector memory CD4+ and CD8+ T cell subsets.
abstract: Interleukin (IL)-7 and its receptor (IL-7Ralpha) play important roles in regulating lymphopoiesis. Previous studies have reported that human immunodeficiency virus-1 (HIV-1) viraemia affects the expression of IL-7Ralpha, but its effects on CD4+ and CD8+ T cell memory subsets have not been studied. Using eight-colour flow cytometry, we compared the immunophenotypic patterns of CD4+ and CD8+ T cell subsets expressing IL-7Ralpha and activation markers, as well as circulating IL-7 levels, in three well-defined groups of HIV-1-infected subjects: successfully treated, viraemic and long-term non-progressor (LTNP). Compared with successfully treated and LTNP subjects, viraemic patients had reduced expression of IL-7Ralpha on both CD4+ and CD8+ T cells, particularly on central and effector memory T cell compartments, and substantially elevated expression of activation markers on CD8+ T cell subsets. Circulating IL-7 levels were correlated negatively with the number of CD4+ and CD8+ T cell subsets expressing IL-7Ralpha; these associations were stronger with CD4+ T cell subsets and mainly with central and effector memory cells. The expression of activation markers on CD4+ and CD8+ cell T subsets was not related to circulating IL-7 levels. A strong negative correlation was observed between central memory CD4+ or CD8+ T cells expressing IL-7Ralpha and those expressing activation markers, independently of IL-7 levels. Collectively, these results provide further insight on the role of unsuppressed viral load in disrupting the IL-7/IL-7Ralpha system and contributing to HIV-1 disease progression.
authors.affiliation: Immunodeficiency Service, Montreal Chest Institute, Montreal, Quebec, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Mercier
authors.forename: M-R
authors.initials: MR
authors.lastname: Boulassel
authors.forename: B
authors.initials: B
authors.lastname: Yassine-Diab
authors.forename: C
authors.initials: C
authors.lastname: Tremblay
authors.forename: N-F
authors.initials: NF
authors.lastname: Bernard
authors.forename: R-P
authors.initials: RP
authors.lastname: Sekaly
authors.forename: J-P
authors.initials: JP
authors.lastname: Routy
mesh_terms: D000956:Antigens, Viral / Q000097:blood*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000097:blood; D053699:Interleukin-7 Receptor alpha Subunit / Q000097:blood*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019562:Viral Load
chemical_list: D000956:Antigens, Viral; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit