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Cutting Edge: CD28 controls dominant regulatory T cell activity during active immunization.
Clay Lyddane1, Beata U Gajewska, Elmer Santos
1Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 7, 2006
Summary
CD28 signaling is crucial for T cell survival but does not prevent regulatory T cell dominance. Adjuvant immunization overcomes this, with CD28 regulating antigen-induced immunoregulation.
Area of Science:
- Immunology
- T cell biology
- Immune regulation
Background:
- CD28 ligation during antigen recognition is vital for effective T cell responses.
- The role of CD28 in controlling peripheral regulatory T cell function is not well understood.
Purpose of the Study:
- To investigate the role of CD28 in the development and function of regulatory T cells in vivo.
- To determine if CD28 signaling is sufficient to prevent regulatory T cell dominance.
Main Methods:
- Naive wild-type or CD28(-/-) CD4(+)CD25(-) T cells were exposed to peptide in vivo.
- Regulatory activity was assessed by adoptively transferring primed T cells and challenging with an immunogen.
- The effect of adjuvant immunization on regulatory dominance and Foxp3 expression was evaluated.
Main Results:
- In vivo peptide exposure induced regulatory T cell activity in naive T cells, suppressing subsequent responses.
- CD28 engagement during priming was essential for T cell survival but insufficient to prevent regulatory dominance.
- Adjuvant immunization abrogated regulatory dominance and reduced Foxp3 expression in a CD28-dependent manner.
Conclusions:
- CD28 signaling is critical for T cell survival and licensing active immunization.
- CD28 plays a key role in regulating antigen-induced immunoregulation, preventing unchecked regulatory T cell function.