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Updated: Aug 8, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 16, 2013
CD4(+) and CD8(+) T cell death during human immunodeficiency virus infection in vitro
J Blanco1, J Barretina, C Cabrera
1Fundació irsiCaixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Ctra. Canyet s/n, Badalona, Catalonia, 08916, Spain. jbalanco@ns.hugtip.scs.es
Insights
Human immunodeficiency virus (HIV) infection affects T-cell death differently. X4 HIV strains cause more CD4(+) T-cell death and can also impact CD8(+) T-cell viability, unlike R5 strains.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus (HIV) infects CD4(+) T cells, leading to immune deficiency.
- Understanding the differential impact of HIV strains on immune cells is crucial for therapeutic development.
Purpose of the Study:
- To evaluate the death of CD4(+) and CD8(+) T cells during in vitro HIV infection.
- To compare the effects of X4 and R5 HIV isolates on T-cell viability in peripheral blood mononuclear cells (PBMC) and tonsilar tissue.
Main Methods:
- In vitro infection of human PBMCs and tonsilar tissue with various X4 and R5 HIV isolates.
- Assessment of CD4(+) and CD8(+) T-cell viability and death rates post-infection.
- Analysis of the role of the HIV env gene and viral replication in T-cell death.
Main Results:
- Acute HIV infection decreased T-cell viability, with X4 isolates causing higher rates of CD4(+) T-cell death compared to R5 isolates.
- The X4 isolate AOM induced significantly more CD4(+) T-cell death than laboratory X4 or R5 isolates.
- CD8(+) T-cell viability was affected only by X4 viruses, dependent on the env gene and productive HIV replication in CD4(+) cells.
Conclusions:
- X4 and R5 HIV isolates differentially deplete CD4(+) T cells.
- CD8(+) T-cell viability can be compromised by X4 HIV through mechanisms distinct from those affecting CD4(+) T cells.
Abstract:
We have evaluated the death of CD4(+) and CD8(+) T cells during in vitro human immunodeficiency virus (HIV) infection of peripheral blood mononuclear cells (PBMC) and tonsilar tissue. Acute infections with several X4 and R5 HIV isolates induced a decrease in cell viability that was higher in infections with X4 viruses and correlated with an increased rate of CD4(+) T-cell death. In CD4(+) T cells, the primary X4 isolate AOM induced higher levels of death than the laboratory X4 isolates IIIB and NL4-3 or the R5 isolates BaL and MDM. An effect on CD8(+) T-cell viability was exclusively observed in infections by X4 viruses, including the NL4-3 strain, in both PBMC and tonsilar tissue. This effect was dependent on the env gene of the infecting isolate and required productive HIV replication in CD4(+) but not in CD8(+) T cells. Our results suggest that X4 and R5 HIV isolates depleted CD4(+) T cells to a different extent and that CD8(+) T-cell viability may also be affected by mechanisms other than those acting in CD4(+) T cells.
