Journal article
Survival defects and skewed memory phenotype of HIV-specific CD8+ T cells are detectable in early clinical stages of chronic HIV infection
Journal of neurovirology, Vol.12
01 May 2006
Abstract
HIV-specific CD8+ T cells have been shown to be mainly of the CD45RA-CD62L- effector memory phenotype and are highly sensitive to spontaneous and CD95/Fas-induced apoptosis. In this study, we examined the memory phenotype (CD45RA-CD62L+ central memory CD8+ T cells, CD45RA-CD62L- and CD45RA+CD62L- effector memory CD8+ T cells) and apoptosis sensitivity (spontaneous and CD95-induced) of HIV-specific CD8+ T cells from 39 HIV-infected individuals to determine the clinical correlates of skewed memory phenotype and increased apoptosis sensitivity. No correlation was observed between percentages and absolute numbers of HIV-specific CD8+ T cell memory subpopulations and total CD4+ T cell counts, viral load and disease duration. Skewed phenotype and statistically significant differences in the ratio of CD45RA-CD62L- and CD45RA+CD62L- effector memory CD8+ T cells was found already in patients of clinical stage A1 when HIV-specific CD8+ T cells, CMV-specific CD8+ T cells and total CD8+ T cells were compared. That ratio was 10.8 for HIV-specific CD8+ T cells, 3.1 for CMV-specific CD8+ T cells and 1.8 for total CD8+ T cells. When HIV-specific CD8+ T cells were compared across clinical stages, higher absolute HIV-specific CD8+ T cells of both effector memory subpopulations were found in A1 compared to A2 and A3, however, the ratio between the two effector memory populations was not different between these clinical stages. When spontaneous and CD95-induced apoptosis sensitivity was analyzed, no correlation was observed between apoptosis sensitivity and total CD8 count, viral load and disease duration. However, a statistically significant inverse correlation was found between the percentage of CD95-induced apoptosis and total CD4 counts. A statistically significant increase in apoptosis sensitivity for both spontaneous and CD95-induced was already found in clinical stage A1 when HIV-specific CD8+ T cells were compared to total CD8+ T cells and CMV- and EBV-specific CD8+ T cells and argues against chronic antigenic stimulation as a mechanism responsible for apoptosis sensitivity. Our data indicate that the skewed memory phenotype and increased apoptosis sensitivity of HIV-specific CD8+ T cells is already present at early stages of chronic HIV disease and does not correlate with disease duration and viral load.
Metrics
1 Record Views
Details
- Title
- Survival defects and skewed memory phenotype of HIV-specific CD8+ T cells are detectable in early clinical stages of chronic HIV infection
- Creators
- Y MuellerC PetrovasS R AltorkJ SainiP PitsakisK MounzerJ AltmanP Katsikis
- Publication Details
- Journal of neurovirology, Vol.12
- Resource Type
- Journal article
- Language
- English
- Identifiers
- 991019339573004721