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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Longitudinal analysis of CD8(+) T-cell phenotype and IL-7, IL-15 and IL-16 mRNA expression in different tissues
P Caufour1, R Le Grand, A Chéret
1CEA, service de neurovirologie, DSV/DRM, CRSSA, institut Paris-Sud sur les cytokines, Fontenay-aux-Roses, France.
Abstract:
Infection of macaques with pathogenic isolates of simian immunodeficiency virus (SIV) represents a useful model of HIV infection that offers the unique opportunity to investigate the very early modifications that affect CD8(+) T-lymphocyte subsets and related cytokines during lentiviral infection. Herein, three cynomolgus macaques were inoculated intravenously with a pathogenic isolate of SIVmac 251. In fresh isolated mononuclear cells from blood, lymph node and bronchoalveolar lavage, we analyzed changes in the phenotype of CD8(+) T cells and we used reverse transcription-PCR to monitor the expression of IL-7, IL-15 and IL-16 mRNA. We demonstrated that an expansion of CD8(+)CD28(-) T cells occurs from the third week of infection on in the peripheral blood and in the lung, whereas CD8(+)CD28(+) T cells expand in the lymph nodes. Concomitantly, we evidenced mRNA modulations in IL-16, IL-15 and IL-7 expression in the three compartments studied. The containment of systemic viral replication was associated with an overexpression of IL-16 mRNA in the lung and in the peripheral blood. Given the immunomodulatory properties of IL-15 and IL-7 and the potential antiviral ability of IL-16, these perturbations could have important implications in early viral dissemination and HIV immunopathogenesis.
Insights
Simian immunodeficiency virus (SIV) infection in macaques reveals early CD8(+) T-cell subset changes and cytokine mRNA alterations. These findings offer insights into lentiviral infection dynamics and HIV immunopathogenesis.
Area of Science:
- Immunology
- Virology
- Primatology
Background:
- Simian immunodeficiency virus (SIV) infection in macaques serves as a critical model for studying human immunodeficiency virus (HIV) infection.
- Investigating early changes in CD8(+) T-lymphocyte subsets and cytokines during lentiviral infection is crucial for understanding disease progression.
Purpose of the Study:
- To analyze early modifications in CD8(+) T-lymphocyte subsets and cytokine mRNA expression in macaques infected with SIV.
- To explore the relationship between viral replication, T-cell subset changes, and cytokine profiles in different tissues.
Main Methods:
- Three cynomolgus macaques were intravenously inoculated with SIVmac 251.
- Phenotypic analysis of CD8(+) T cells was performed on mononuclear cells from blood, lymph nodes, and bronchoalveolar lavage.
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to monitor mRNA expression of Interleukin-7 (IL-7), Interleukin-15 (IL-15), and Interleukin-16 (IL-16).
Main Results:
- An expansion of CD8(+)CD28(-) T cells was observed in peripheral blood and lungs from the third week post-infection.
- CD8(+)CD28(+) T cells expanded in lymph nodes.
- Modulations in IL-16, IL-15, and IL-7 mRNA expression were detected across all studied compartments.
- Overexpression of IL-16 mRNA in the lung and peripheral blood correlated with containment of systemic viral replication.
Conclusions:
- Early SIV infection induces distinct CD8(+) T-cell subset expansions in different anatomical sites.
- Altered expression of IL-7, IL-15, and IL-16 suggests their involvement in early viral dissemination.
- These cytokine perturbations may play a significant role in the immunopathogenesis of HIV infection.
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