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A pertussis toxin-sensitive process controls thymocyte emigration.

K E Chaffin1, R M Perlmutter

  • 1Howard Hughes Medical Institute, University of Washington, Seattle 98195.

European Journal of Immunology
|October 1, 1991
PubMed
Summary
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This study reveals a novel pathway essential for T cell emigration from the thymus. Pertussis toxin (PT)-sensitive signaling involving Gi proteins is crucial for mature T cells to migrate to peripheral lymphoid organs.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Signaling

Background:

  • Peripheral T cells originate from bone marrow progenitors and mature in the thymus.
  • The mechanism of thymocyte egress to peripheral compartments remains largely unknown.
  • Pertussis toxin (PT) sensitivity suggests involvement of Gi protein signaling.

Purpose of the Study:

  • To investigate the role of PT-sensitive signaling in thymocyte emigration.
  • To identify the molecular mechanisms governing T cell migration from the thymus.

Main Methods:

  • Generation of transgenic lck-PT mice expressing PT in thymocytes.
  • Analysis of T cell populations in thymus and peripheral lymphoid organs.
  • Assessment of cell surface phenotype, allogeneic responses, and in vivo homing assays.

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Main Results:

  • Mature T lineage cells accumulated in lck-PT thymuses.
  • These cells failed to populate peripheral lymphoid organs despite normal phenotype and allogeneic responses.
  • Defective in vivo homing was observed, independent of common homing receptors or cAMP levels.

Conclusions:

  • A novel PT-sensitive signaling pathway, likely involving Gi proteins, is critical for thymocyte emigration.
  • This pathway is essential for T cell migration from the thymus to peripheral tissues.