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Differential effects of CD28 costimulation upon cytokine production by CD4+ and CD8+ T cells
Rosemary Rochford1, James E Riggs, Anaira Clavo
1Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse University, Syracuse, NY 13210, USA.
Insights
CD28 costimulation boosts T cell proliferation and cytokine release, particularly in CD4+ T cells. Naive CD4+ T cells show the strongest response, indicating distinct CD28-driven differentiation pathways.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD28 is a crucial costimulatory receptor on T lymphocytes.
- Understanding CD28's role in T cell activation is vital for immunotherapy.
Purpose of the Study:
- To investigate the impact of CD28 ligation on CD4+ and CD8+ T cell proliferation and cytokine production.
- To differentiate the CD28 response between naive and memory/effector T cell subsets.
Main Methods:
- Assessment of T lymphocyte proliferation and cytokine production following CD28 ligation.
- Subdivision of CD4+ and CD8+ T cells into CD44lo (naïve) and CD44hi (memory/effector) populations.
Main Results:
- CD28 costimulation enhanced proliferation in both CD4+ and CD8+ T cells.
- Cytokine production, including IL-2, IL-3, IFN-γ, and GM-CSF, increased significantly, especially in CD4+ T cells.
- Naive CD4+ T cells exhibited the highest responsiveness to CD28 ligation.
Conclusions:
- CD28 costimulation differentially impacts CD4+ and CD8+ T cell responses.
- Distinct differentiation programs are initiated by CD28-mediated costimulation in CD4+ versus CD8+ T cells.
Abstract:
The impact of CD28 ligation upon CD4+ and CD8+ T lymphocyte proliferation and cytokine production was assessed. Although costimulation increased the proliferative response of both T cell subsets, cytokine production was most markedly increased in the CD4+ subset, as evidenced by a 40-fold increase in interleukin-2 (IL-2), a 14-fold increase in interleukin-3 (IL-3) and 5-fold increases in interferon gamma and GM-colony-stimulating factor (CSF) production. The CD8+ T cell response to CD28 ligation was less marked, maxima being a 5-fold increase in IL-2 production and 2-fold increases in IL-3 and GM-CSF production. Resolution of CD4+ and CD8+ T cells into their CD44lo (naïve) and CD44hi (memory/effector) subsets revealed that naive CD4+ T cells were the most CD28-responsive subsets. CD28-mediated costimulation promotes distinct differentiation programs in CD4+ versus CD8+ T cells.
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