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CD28 costimulation and T lymphocyte proliferative responses in HIV-1 infection
M Carlesimo1, O Pontesilli, A R Varani
1Department of Clinical Medicine, University of Rome La Sapienza, Italy.
Insights
The CD28 costimulation pathway remains intact during HIV-1 infection, even as T cell responses decline. This suggests HIV-specific T cells are not deleted but lack sufficient priming in infected individuals.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- T lymphocyte dysfunction is a hallmark of advanced HIV-1 infection.
- Costimulatory signals are crucial for optimal T cell activation.
- The role of CD28 costimulation in HIV-1 infection requires further elucidation.
Purpose of the Study:
- To determine if defective costimulatory signals contribute to T cell dysfunction in HIV-1 infection.
- To assess the impact of CD28 costimulation on T cell responses to HIV-1 antigens.
Main Methods:
- Investigated CD28 costimulation effects on T cell receptor/CD3-induced proliferation.
- Assessed CD28 costimulation on HIV-1 antigen (gp160, p24)-induced proliferation.
- Compared responses in HIV-1 infected individuals across different disease stages and HIV-1- subjects.
Main Results:
- CD3-mediated T cell responses decreased with advanced HIV-1 stages.
- CD28 costimulation effectively enhanced T cell responses at all HIV-1 stages.
- Enhanced T cell responses to HIV-1 antigens with CD28 costimulation were observed only in subjects with pre-existing responses, such as those immunized with gp160.
Conclusions:
- The CD28 costimulation pathway is functionally intact during HIV-1 infection.
- HIV-specific T cells are likely not deleted but inadequately primed during natural HIV-1 infection.
- CD28 costimulation may offer a potential therapeutic avenue to boost T cell function in HIV-1.
Abstract:
To investigate whether defective costimulatory signals could be involved in the loss of T lymphocyte functions during HIV-1 infection, we tested the effect of CD28 costimulation on both T cell receptor/CD3 and HIV-1 antigen-induced proliferative responses. Although CD3-mediated responses significantly decreased with more advanced stages of HIV-1 infection, the ability of potentiating the responses through CD28 costimulation was maintained at all stages and did not differ from that of HIV-1- subjects. When CD28 costimulation was studied in lymphocyte cultures stimulated with HIV-1 gp160 or p24, potentiation was seen only when a significant response was present without additional CD28 triggering, namely in subjects receiving active immunization with recombinant gp160. These results confirm the integrity of the CD28 pathway of costimulation during HIV-1 infection, and suggest that lymphocytes responding to soluble HIV-1 antigen are not deleted in HIV-1-infected patients, but do not receive significant priming during the natural course of the infection.