T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis
✍ Scribed by Ryan M. Cinalli; Catherine E. Herman; Brian O. Lew; Heather L. Wieman; Craig B. Thompson; Jeffrey C. Rathmell
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 329 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
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 Gαi‐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.