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Published on: May 30, 2013
HIV-related alterations in CD8 cell subsets defined by in vitro survival characteristics
1American Red Cross Blood Services, Los Angeles, California 90006.
Insights
In HIV infection, interleukin-2 (IL2) enhances CD8 cell survival. Activated CD8 cells in HIV patients show distinct survival patterns, with some requiring IL2 and others being non-viable even with IL2.
Area of Science:
- Immunology
- Virology
Background:
- Over 50% of CD8 cells from HIV-infected individuals exhibit poor survival in vitro.
- This CD8 cell loss is more pronounced in activated subsets.
- Cytokines were investigated for their potential to enhance CD8 cell survival.
Purpose of the Study:
- To determine if cytokines can improve CD8 cell survival in HIV-infected individuals.
- To characterize the survival patterns of CD8 cell subsets in the presence of interleukin-2 (IL2).
Main Methods:
- In vitro culture of peripheral blood mononuclear cells from HIV-infected and control groups.
- Assessment of CD8 cell survival in medium alone and with various cytokines (IL1, IL2, IL4, IL6, TNF, IFN-γ).
- Dual-color flow cytometry to analyze CD8 cell phenotypes (Leu8, CD45RA, HLA-DR, CD57, CD38).
Main Results:
- Only IL2 significantly enhanced CD8 cell survival in the HIV group compared to controls.
- Three CD8 subsets were identified: survivors, IL2-dependent survivors, and nonsurvivors.
- HIV-infected individuals had a higher proportion of non-surviving CD8 cells with activated phenotypes (Leu8-, CD57+, HLA-DR+).
Conclusions:
- IL2 is a key cytokine for enhancing CD8 cell survival in HIV infection.
- Activated CD8 cells in HIV are heterogeneous, comprising IL2-dependent and IL2-independent non-survivors.
- The non-surviving activated CD8 cells in HIV represent an abnormal subset with impaired viability.
Abstract:
Previously we showed that over 50% of CD8 cells from HIV-infected persons do not survive in 3-day cultures of mononuclear cells; this loss occurred preferentially in subsets with phenotypes indicative of in vivo activation. In the studies reported here, we asked if cytokines enhanced CD8 cell survival. Of IL1, IL2, IL4, IL6, tumor necrosis factor, and interferon-gamma only IL2 specifically enhanced CD8 survival in the HIV group, compared to the control group. Further studies thus focused on characterizing CD8 cell survival in the presence of IL2. In both study groups, three subsets of CD8 cells were identified based on in vitro survival: (a) those surviving in culture medium alone (survivors), (b) those surviving only when IL2 was included in the culture medium (IL2-dependent survivors), and (c) those failing to survive even in the presence of IL2 (nonsurvivors). By dual-color cytofluorometry, the CD8 survivor subset was similar in the two study groups, and expressed nonactivated phenotypes (Leu8+, CD45RA+, HLA-DR-). The IL2-dependent survivor subset was also similar in the two study groups and expressed the phenotypes Leu8-, CD45RA+, CD57+, HLA-DR+, and CD38+, suggesting prior activation. The CD8 nonsurvivor subset, in contrast, was markedly different in the study groups: compared to the control group, the HIV group contained significantly higher proportions of CD8 cells expressing the phenotypes Leu8-, CD57+, and HLA-DR+, also suggesting activation. These findings indicate that, in HIV infection, the activated CD8 cell subsets that do not survive in medium alone consist of a "normal" component that requires IL2 for survival and an "abnormal" component that does not survive even in IL2.
