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Predominant involvement of CD8+CD28- lymphocytes in human immunodeficiency virus-specific cytotoxic activity
S Fiorentino1, M Dalod, D Olive
1Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, Unité 445 de l'Institut National de la Santé et de la Recherche Médicale, Hôpital Cochin, Paris, France.
Insights
Distinct human immunodeficiency virus (HIV) CD8+ T-cell populations have unique functions. The CD8+CD28- subset mediates HIV-specific cytotoxic activity, while the CD8+CD28+ subset inhibits viral replication non-cytotoxically.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Distinct functional CD8+ T-cell subsets exist during human immunodeficiency virus (HIV) infection.
- The CD8+CD28+ subpopulation mediates non-cytotoxic inhibition of HIV replication.
- CD8+ T cells also exhibit HIV-specific cytotoxic activity.
Purpose of the Study:
- To characterize the functional roles of CD8+ T-cell subsets in HIV infection.
- To identify the specific CD8+ T-cell population responsible for HIV-specific cytotoxic activity.
- To assess the proliferative capacity and sustained cytotoxicity of these subsets.
Main Methods:
- Isolation and purification of CD8+CD28- and CD8+CD28+ T-cell populations from peripheral blood of HIV-infected individuals.
- Assessment of HIV-specific cytotoxic activity immediately after cell purification.
- In vitro restimulation of CD8+CD28- cells with autologous blast cells to evaluate proliferation and sustained cytotoxicity.
- In vitro generation of HIV-specific cytotoxic T cells from the CD8+CD28+ population.
Main Results:
- The CD8+CD28- lymphocyte population displays immediate HIV-specific cytotoxic activity upon purification.
- The CD8+CD28- population retains its cytotoxic function and exhibits proliferation after in vitro restimulation.
- HIV-specific cytotoxic T cells can be generated in vitro from the CD8+CD28+ T-cell population.
Conclusions:
- The CD8+CD28- T-cell subset is the primary mediator of direct HIV-specific cytotoxic activity.
- The CD8+CD28- subset possesses functional plasticity, including proliferation and sustained cytotoxicity.
- While CD8+CD28+ cells primarily inhibit replication non-cytotoxically, they can also be a source of cytotoxic T cells under specific in vitro conditions.
Abstract:
Distinct functional CD8+ T-cell populations have been observed during human immunodeficiency virus (HIV) infection. One of these functions is the inhibition of viral replication by a noncytotoxic mechanism, which was shown to be mediated by the CD8+CD28+ subpopulation. On the other hand, CD8+ T cells exert an HIV-specific cytotoxic activity. The present study shows that CD8+CD28- lymphocytes display this HIV-specific cytotoxic activity, which is detectable immediately after the cells are purified from peripheral blood. The CD28- population is also able to proliferate and to retain its cytotoxic activity after in vitro restimulation with autologous blast cells. Finally, HIV-specific cytotoxic T cells can be obtained in vitro from the CD8+CD28+ population.