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Activation requirements for the induction of CD4+CD25+ T cell suppressor function
Angela M Thornton1, Ciriaco A Piccirillo, Ethan M Shevach
1Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda 20892-1892, USA. athornton@niaid.nih.gov
European Journal of Immunology
|February 10, 2004
Summary
Interleukin-2 (IL-2) and Interleukin-4 (IL-4) are crucial for the in vitro survival and differentiation of CD4(+)CD25(+) T suppressor cells. However, CD28 and CTLA-4 costimulatory signals are not required for their suppressor function.
Area of Science:
- Immunology
- Cell Biology
- T cell differentiation
Background:
- CD4(+)CD25(+) T suppressor cells are vital for immune regulation.
- Their in vivo function relies on IL-2 and CD28 costimulation.
- Understanding in vitro requirements is key to manipulating immune responses.
Purpose of the Study:
- To elucidate the specific cytokine and costimulatory signals needed for CD4(+)CD25(+) T cell activation and suppressor function in vitro.
- To investigate the roles of IL-2, IL-4, and costimulatory molecules (CD28, CTLA-4) in T suppressor cell development.
Main Methods:
- A two-stage in vitro culture system was established.
- CD4(+)CD25(+) T cells were activated in the primary culture.
- Suppressor function was assessed by co-culturing activated cells with responder cells.
Main Results:
- Pre-culture with anti-CD3 and IL-2 or IL-4 promoted CD4(+)CD25(+) T cell proliferation and potent suppressor function.
- IL-6, IL-7, IL-9, IL-10, and IL-15 did not support suppressor activity.
- Inhibition of CD28/CTLA-4 interactions did not impair suppressor function induction or activity.
Conclusions:
- IL-2 and IL-4 are essential for the survival and differentiation of CD4(+)CD25(+) T cells into functional suppressor cells in vitro.
- CD28/CTLA-4-mediated costimulation is not required for the induction or function of these T suppressor cells under the tested conditions.