Persistent human immunodeficiency virus-1 antigenaemia affects the expression of interleukin-7Ralpha on central and effector memory CD4+ and CD8+ T cell subsets.
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.
Mercier
F
F
Immunodeficiency Service, Montreal Chest Institute, Montreal, Quebec, Canada.
Boulassel
M-R
MR
Yassine-Diab
B
B
Tremblay
C
C
Bernard
N-F
NF
Sekaly
R-P
RP
Routy
J-P
JP
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
D000956:Antigens, Viral; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit