Changes in function of HIV-specific T-cell responses with increasing time from infection.
Recently HIV-infected individuals have virus-specific responses characterized by IFN-gamma/IL-2 secretion and proliferation rarely seen in chronic infection. To investigate the timing of loss of HIV-specific T-cell function, we screened cells from 59 treatment-naïve HIV-infected individuals with known dates of infection for proteome-wide responses secreting IFN-gamma/IL-2 and IFN-gamma alone by ELISPOT. HIV peptide-specific proliferation was assessed by carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution. The contribution of IFN-gamma/IL-2 and IFN-gamma-only secretion to the total HIV-specific response was compared in subjects infected <6, 6-12, and 12-36 mo earlier. The frequency of IFN-gamma/IL-2-secreting cells fell, while that of IFN-gamma-only secretion rose with time from infection. HIV peptide-specific proliferative responses were almost exclusively mediated by CD8(+) T cells, and were significantly lower in cells obtained from the 12-36 mo versus < 6 mo post-infection groups. By the second year of infection there was a significant difference in these functions compared to those assessed within 6 mo.
Ndongala
Michel L
ML
Research Institute of the McGill University Health Center, Montréal, Québec, Canada.
Kamya
Philomena
P
Boulet
Salix
S
Peretz
Yoav
Y
Rouleau
Danielle
D
Tremblay
Cécile
C
Leblanc
Roger
R
Côté
Pierre
P
Baril
Jean-Guy
JG
Thomas
RéJean
R
Vézina
Sylvie
S
Boulassel
Mohamed R
MR
Routy
Jean-Pierre
JP
Sékaly
Rafick P
RP
Bernard
Nicole F
NF
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D010455:Peptides / Q000276:immunology; D020543:Proteome; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D054298:Human Immunodeficiency Virus Proteins; D007376:Interleukin-2; D010455:Peptides; D020543:Proteome; D007371:Interferon-gamma