A pertussis toxin-sensitive process controls thymocyte emigration.
Although it is well known that essentially all peripheral T cells are derived from bone marrow progenitors that mature in the thymus, the mechanism whereby thymocytes gain access to peripheral compartments is obscure. We have learned that this process is sensitive to pertussis toxin (PT). Transgenic lck-PT mice were generated which express the catalytic subunit of PT in all thymocytes. In a previous study we observed that T cell receptor signaling is unimpaired in these cells despite the virtual elimination of their Gi protein signal transduction elements through endogenous PT activity. Here we demonstrate that mature T lineage cells accumulate in lck-PT thymuses and fail to populate peripheral lymphoid organs. The accumulating cells closely resemble normal peripheral T lymphocytes with respect to cell surface phenotype and responses to allogeneic spleen cells, yet perform poorly in in vivo homing assays. This migratory defect does not result from deficient expression of common homing receptors or alterations in intracellular cAMP concentrations. Based on these results, we propose that a novel PT-sensitive signaling pathway, almost certainly involving a Gi protein, is required for thymocyte emigration.
Chaffin
K E
KE
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Perlmutter
R M
RM
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D016516:CD4-CD8 Ratio; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008822:Mice, Transgenic; D037342:Pertussis Toxin; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D011065:Poly(ADP-ribose) Polymerases; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019204:GTP-Binding Proteins