Abnormal antigen receptor-initiated signal transduction in lpr T lymphocytes.
The CD4-, CD8- double-negative (DN) T cells that accumulate in an age-dependent manner in peripheral lymphoid organs of lpr-homozygous mice display deficient activation in response to signals initiated by the antigen-specific T cell receptor (TCR)/CD3 complex. Abnormalities which could contribute to this defect include low expression and rapid TCR/CD3 modulation, loss of CD4, CD8, CD2 and Ly-6.2, aberrant expression of CD45, and constitutive elevations of inositol phospholipid turnover, tyrosine phosphorylation, and expression of the p59fyn protein tyrosine kinase (PTK) and a few other protooncogenes. These properties strongly suggest that DN lpr T cells are chronically activated in vivo, perhaps by some self antigen(s), rendering them refractory to additional in vitro stimulation. Deficient activation of these cells is, therefore, most likely a secondary consequence of the Fas defect whose primary effect is allowing these aberrant cells to escape from the thymus and expand in the periphery.
Altman
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Division of Cell Biology, La Jolla Institute for Allergy and Immunology, CA 92037.
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D008232:Lymphoproliferative Disorders / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism; D019014:fas Receptor
D000954:Antigens, Surface; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; D014443:Tyrosine