Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase

Karen E. Chaffin, Chan R. Beals, Thomas M. Wilkie, Katherine A. Forbush, Melvin I. Simon, Roger M. Perlmutter

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

Stimulation of the T lymphocytic antigen receptor - CD3 complex (TCR-CD3) cause T cell activation by a process associated with increased phosphatidylinositol-specific phospholipase C (PI-PLC) activity. Evidence exists suggesting that GTP-binding (G) proteins, particularly the pertussis toxin (PT)-sensitive G(i) proteins, participate in this signal transduction pathway. To clarify the role of G(i) proteins in TCR-CD3 signaling, and to investigate other possible functions of G(i) molecules in T cells, we expressed the S1 subunit of PT in the thymocytes of transgenic mice using the lymphocyte-specific lck promoter. Transgenic thymocytes contained S1 activity and exhibited profound depletion of G(i) protein PT substrates in a manner suggesting their inactivation by S1 in vivo. Nevertheless, treatment of transgenic thymocytes with mitogenic stimuli provoked normal increases in intracellular free Ca2+ concentrations and IL-2 secretion, indicating that G(i) proteins are not required for T cell activation. These normal signaling responses notwithstanding, mature thymocytes accumulated in lck-PT mice and did not appear in secondary lymphoid organs or in the circulation. Viewed in the context of the known features of Bordetella pertussis infection, our results suggest that a PT-sensitive signaling process, probably involving G(i) proteins, regulates thymocytes emigration.

Original languageEnglish (US)
Pages (from-to)3821-3829
Number of pages9
JournalEMBO Journal
Volume9
Issue number12
DOIs
StatePublished - Jan 1 1990

Keywords

  • G protein
  • T cell antigen receptor
  • T lymphocyte
  • pertussis toxin
  • signal transduction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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