-
Views
-
Cite
Cite
Lucy S K Walker, Helen E Wiggett, Fabrina M C Gaspal, Chandra R Raykundalia, Margaret D Goodall, Kai-Michael Toellner, Peter J L Lane, Established T Cell-Driven Germinal Center B Cell Proliferation Is Independent of CD28 Signaling but Is Tightly Regulated Through CTLA-4, The Journal of Immunology, Volume 170, Issue 1, January 2003, Pages 91–98, https://doi.org/10.4049/jimmunol.170.1.91
Close - Share Icon Share
Abstract
CD4 T cell activation is positively (CD28) and negatively (CTLA-4) regulated by the costimulatory ligands CD80 and CD86. A central question is how the balance between these two opposing forces is controlled as T cells differentiate. We have previously shown that CD28 signaling is absolutely required to prime naive CD4 T cells to differentiate into effectors that provide help for germinal centers and class-switched Ab responses. In this study, we show that the requirement for CD28 signaling is transient and effector CD4 T cells do not require CD28 signals to sustain their function. The CD28 independence of effector T cells within germinal centers suggested that a key function for CD80/CD86 under these circumstances might be to provide negative regulatory signals via the CD28 homologue CTLA-4. By examining germinal center responses in mice where the ability to signal through T cell CTLA-4 was compromised, we provide data that supports a critical role for CTLA-4 in down-regulating T cell help for germinal center B cells.
