Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells.
Publication/Presentation Date
3-1-2008
Abstract
Costimulatory signals are critical to T cell activation, but how their effects are mediated remains incompletely characterized. Here, we demonstrate that locally produced C5a and C3a anaphylatoxins interacting with their G protein-coupled receptors (GPCRs), C5aR and C3aR, on APCs and T cells both upstream and downstream of CD28 and CD40L signaling are integrally involved in T cell proliferation and differentiation. Disabling these interactions reduced MHC class II and costimulatory-molecule expression and dramatically diminished T cell responses. Importantly, impaired T cell activation by Cd80-/-Cd86-/- and Cd40-/- APCs was reconstituted by added C5a or C3a. C5aR and C3aR mediated their effects via PI-3 kinase-gamma-dependent AKT phosphorylation, providing a link between GPCR signaling, CD28 costimulation, and T cell survival. These local paracrine and autocrine interactions thus operate constitutively in naive T cells to maintain viability, and their amplification by cognate APC partners thus is critical to T cell costimulation.
Volume
28
Issue
3
First Page
425
Last Page
435
ISSN
1097-4180
Published In/Presented At
Strainic, M. G., Liu, J., Huang, D., An, F., Lalli, P. N., Muqim, N., Shapiro, V. S., Dubyak, G. R., Heeger, P. S., & Medof, M. E. (2008). Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity, 28(3), 425–435. https://doi.org/10.1016/j.immuni.2008.02.001
Disciplines
Medicine and Health Sciences
PubMedID
18328742
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article