CD4+ T cells in HIV infection show increased levels of expression of a receptor for vasoactive intestinal peptide, VPAC2.
Immune activation is a strong predictor of disease outcome in HIV infection and promotes the loss of CD4+ T cells. The neuropeptide, vasoactive intestinal peptide (VIP), has immune-modulating properties with specific receptors identified on lymphocytes; VPAC1 and VPAC2. Studies have shown that VIP limits immune activation and apoptosis in T cells by decreasing the expression of the apoptosis signaling molecule Fas ligand (FasL). VIP receptor surface expression has not been investigated by flow cytometry in the context of HIV infection and may represent a novel target for immune-modulating therapy. Eighty-seven untreated HIV-infected individuals with CD4 counts >200 and 57 uninfected controls were recruited from a primary health clinic in Cape Town, South Africa. Flow cytometry was used to determine levels of expression of VPAC1 and VPAC2, as well as FasL on CD4+ T cells, and these results were correlated with the immune activation phenotype %CD38+CD8+ T cells. VPAC2 expression was significantly increased in the HIV group (mean %VPAC2+CD4+ cells 19.25 vs. control 12.56; p ≤ 0.0001), but no difference in VPAC1 expression was observed. VPAC2 correlated positively with FasL (r = 0.310; p = 0.001), and there was a significant inverse correlation between FasL and the CD4 count (r = -0.211; p = 0.013) and a direct correlation with %CD38+CD8+ T cells (r = 0.39; p ≤ 0.0001). Thus, higher levels of immune activation correlated with higher levels of the death-signaling FasL and lower CD4 counts. VPAC2 may provide a novel target for the selective limitation of CD4+ T-cell death in HIV infection.
Division of Haematology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service (NHLS), Tygerberg Hospital, 9th Floor Gold Avenue Rm 47, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa, hipp@sun.ac.za.
Hayley
H
Ipp
Bongani B
BB
Nkambule
Timothy D
TD
Reid
Dalene
D
de Swardt
Linda-Gail
LG
Bekker
Richard H
RH
Glashoff
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D053222:Fas Ligand Protein / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000276:immunology*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000276:immunology; D055815:Young Adult
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D051997:ADP-ribosyl Cyclase 1