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T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis.

Publication ,  Journal Article
Cinalli, RM; Herman, CE; Lew, BO; Wieman, HL; Thompson, CB; Rathmell, JC
Published in: Eur J Immunol
March 2005

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.

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Published In

Eur J Immunol

DOI

ISSN

0014-2980

Publication Date

March 2005

Volume

35

Issue

3

Start / End Page

786 / 795

Location

Germany

Related Subject Headings

  • T-Lymphocytes
  • Receptors, G-Protein-Coupled
  • Receptors, Cytokine
  • Receptors, Antigen, T-Cell
  • Pertussis Toxin
  • Mice
  • Lymphoid Tissue
  • Interleukin-7
  • Immunology
  • Homeostasis
 

Citation

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Cinalli, R. M., Herman, C. E., Lew, B. O., Wieman, H. L., Thompson, C. B., & Rathmell, J. C. (2005). T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis. Eur J Immunol, 35(3), 786–795. https://doi.org/10.1002/eji.200425729
Cinalli, Ryan M., Catherine E. Herman, Brian O. Lew, Heather L. Wieman, Craig B. Thompson, and Jeffrey C. Rathmell. “T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis.Eur J Immunol 35, no. 3 (March 2005): 786–95. https://doi.org/10.1002/eji.200425729.
Cinalli RM, Herman CE, Lew BO, Wieman HL, Thompson CB, Rathmell JC. T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis. Eur J Immunol. 2005 Mar;35(3):786–95.
Cinalli, Ryan M., et al. “T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis.Eur J Immunol, vol. 35, no. 3, Mar. 2005, pp. 786–95. Pubmed, doi:10.1002/eji.200425729.
Cinalli RM, Herman CE, Lew BO, Wieman HL, Thompson CB, Rathmell JC. T cell homeostasis requires G protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis. Eur J Immunol. 2005 Mar;35(3):786–795.
Journal cover image

Published In

Eur J Immunol

DOI

ISSN

0014-2980

Publication Date

March 2005

Volume

35

Issue

3

Start / End Page

786 / 795

Location

Germany

Related Subject Headings

  • T-Lymphocytes
  • Receptors, G-Protein-Coupled
  • Receptors, Cytokine
  • Receptors, Antigen, T-Cell
  • Pertussis Toxin
  • Mice
  • Lymphoid Tissue
  • Interleukin-7
  • Immunology
  • Homeostasis