T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis.
Journal Article (Journal Article)
Signals that regulate T cell homeostasis are not fully understood. G protein-coupled receptors (GPCR), such as the chemokine receptors, may affect homeostasis by direct signaling or by guiding T cell migration to distinct location-restricted signals. Here, we show that blockade of Galphai-associated GPCR signaling by treatment with pertussis toxin led to T cell atrophy and shortened life-span in T cell-replete hosts and prevented T cell homeostatic growth and proliferation in T cell-deficient hosts. In vitro, however, neither GPCR inhibition nor chemokine stimulation affected T cell atrophy, survival, or proliferation. These findings suggest that GPCR signals are not trophic stimuli, but instead may be required for migration to distinct trophic signals, such as IL-7 or self-peptide/MHC. Surprisingly, while chemokines did not affect atrophy, atrophic T cells displayed increased chemokine-induced chemotaxis that was prevented by IL-7 and submitogenic anti-CD3 antibody treatment. This increase in migration was associated with increased levels of GTP-bound Rac and the ability to remodel actin. These data suggest a novel mechanism of T cell homeostasis wherein GPCR may promote T cell migration to distinct location-restricted homeostatic trophic cues for T cell survival and growth. Homeostatic trophic signals, in turn, may suppress chemokine sensitivity and cytoskeletal remodeling, to inhibit further migration.
Full Text
Duke Authors
Cited Authors
- Cinalli, RM; Herman, CE; Lew, BO; Wieman, HL; Thompson, CB; Rathmell, JC
Published Date
- March 2005
Published In
Volume / Issue
- 35 / 3
Start / End Page
- 786 - 795
PubMed ID
- 15719365
Pubmed Central ID
- PMC2628485
International Standard Serial Number (ISSN)
- 0014-2980
Digital Object Identifier (DOI)
- 10.1002/eji.200425729
Language
- eng
Conference Location
- Germany