IL-7-dependent STAT-5 activation and CD8+ T cell proliferation are impaired in HIV infection.

Abstract

This study tests the hypothesis that IL-7 signaling and activity of CD8(+) T cells are impaired in HIV infection. IL-7 is necessary for optimal CTL activity and T cell survival and proliferation. Defects in IL-7R signaling may contribute to impaired activity of IL-7 observed in progressive HIV disease. A decreased proportion of CD8(+) T cells expressing the IL-7Rα chain (CD127) in progressive HIV disease would be expected to affect IL-7 activity. Alternatively, disease-associated defects of remaining CD8(+)CD127(+) T cells may influence IL-7 responsiveness. Therefore, the IL-7 responsiveness of CD8(+)CD127(+) T cells from HIV(-) and untreated or treated HIV(+) individuals was investigated. Blood was collected from HIV(-) and untreated or effectively treated HIV(+) (<50 viral copies/ml for >1 year) individuals, and CD8(+)CD127(+) T cells were isolated and cultured with IL-7. Indicators of IL-7 signaling (P-STAT5) and activity (Bcl-2 and proliferation) were evaluated by flow cytometry. Isolated CD8(+)CD127(+) T cells from untreated HIV(+) individuals expressed significantly less P-STAT5 in response to IL-7 compared with CD8(+)CD127(+) T cells from HIV(-) individuals. In effectively treated HIV(+) individuals, CD8(+)CD127(+) T cells also expressed significantly lower levels of P-STAT5 compared with HIV(-) individuals. IL-7-dependent proliferation of CD8(+)CD127(+) T cells from untreated HIV(+) individuals was similarly impaired. In contrast, IL-7-induced Bcl-2 expression was not impaired in CD8(+)CD127(+) T cells from HIV(+) individuals. These data demonstrate that IL-7/IL-7R dysfunction in HIV infection may contribute to IL-7-specific signaling defects. Decreased, IL-7-dependent activation of STAT5 and impaired proliferation may negatively impact the maintenance of CD8(+) T cell responsiveness in HIV infection.

• Authors: Agatha Vranjkovic, Angela M Crawley, Andrea Patey, Jonathan B Angel
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 89 Issue 4 Pg. 499-506 (Apr 2011) ISSN: 1938-3673 [Electronic] United States
• PMID: 21177484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-7
• Interleukin-7 Receptor alpha Subunit
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Interleukin-7
• STAT5 Transcription Factor

Topics

• Adult
• CD8-Positive T-Lymphocytes (immunology)
• Cross-Sectional Studies
• Female
• Flow Cytometry
• HIV Infections (immunology)
• HIV-1 (pathogenicity)
• Humans
• Interleukin-7 (pharmacology)
• Interleukin-7 Receptor alpha Subunit (metabolism)
• Lymphocyte Activation
• Male
• Middle Aged
• Phosphorylation
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Receptors, Interleukin-7 (metabolism)
• STAT5 Transcription Factor (metabolism)
• Signal Transduction