Increased plasma interleukin-7 level correlates with decreased CD127 and Increased CD132 extracellular expression on T cell subsets in patients with HIV-1 infection.
BACKGROUND
Interleukin (IL)-7 levels are increased in patients with human immunodeficiency virus type 1 (HIV-1)-associated lymphopenia; however, the effects of this on IL-7 receptor (IL-7R) expression, disease progression, and immune reconstitution remain unclear.


METHODS
Plasma IL-7 levels were measured, by enzyme-linked immunoassay, in patients with primary, chronic, or long-term nonprogressive HIV-1 infection (PHI, CHI, and LTNP, respectively) before and after 40-48 weeks of antiretroviral therapy (ART). Cell-surface expression and intracellular expression of the IL-7R components CD127 and CD132 were measured by flow cytometry. The effects of IL-7 and cycloheximide on IL-7R expression by peripheral blood mononuclear cells were examined in vitro.


RESULTS
Plasma IL-7 levels were increased in both patients with PHI and those with CHI; administration of ART resulted in normalized plasma IL-7 levels in patients with PHI but not in those with CHI. Plasma IL-7 levels positively correlated with CD4(+) T cell immune reconstitution in patients with PHI. In vitro, exogenous IL-7 rapidly down-regulated cell-surface CD127 expression, but not CD132 expression, whereas subsequent reexpression required active protein synthesis. HIV-1 infection resulted in progressive decreases in the CD127(+)132(-) subset and increases in the CD127(-)132(+) subset of CD4(+) and CD8(+) T cells. Changes in CD4(+) T cell expression of IL-7R components were evident in patients with LTNP who lost viral control, and these changes preceded increases in plasma IL-7 levels.


CONCLUSIONS
Perturbations in the IL-7/IL-7R system were clearly associated with disease progression but did not reliably predict immune reconstitution.
Sasson
Sarah C
SC
National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia. s.sasson@cfi.unsw.edu.au
Zaunders
John J
JJ
Zanetti
Giulia
G
King
Eleanor M
EM
Merlin
Kate M
KM
Smith
Don E
DE
Stanley
Keith K
KK
Cooper
David A
DA
Kelleher
Anthony D
AD
D049109:Cell Proliferation; D018450:Disease Progression; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7 / Q000097:blood* / Q000276:immunology; D018123:Receptors, Interleukin / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets
C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7