Restoration of thymopoiesis in pT alpha-/- mice by anti-CD3epsilon antibody treatment or with transgenes encoding activated Lck or tailless pT alpha.
Mice deficient for the pre-TCR alpha (pT alpha) chain cannot form a pre-T cell receptor (TCR) and exhibit a severe defect in early T cell development, characterized by lack of "beta selection" and impaired generation of double-positive (DP) thymocytes. Here, we demonstrate that intraperitoneal injection of CD3epsilon-specific antibodies into pT alpha-/- x RAG-/- mice or introduction of an activated p56(lck) transgene in pT alpha-/- mice fully restores the number of DP thymocytes, and that expression of a transgenic pT alpha chain lacking its cytoplasmic portion can overcome all developmental defects associated with pT alpha deficiency. These results allow a better definition of the role of pT alpha in pre-TCR signal transduction and provide conclusive evidence that the cytoplasmic tail of pT alpha is not essential for pre-TCR signaling.
Fehling
H J
HJ
Basel Institute for Immunology, Switzerland.
Iritani
B M
BM
Krotkova
A
A
Forbush
K A
KA
Laplace
C
C
Perlmutter
R M
RM
von Boehmer
H
H
D000818:Animals; D017252:CD3 Complex / Q000502:physiology*; D002454:Cell Differentiation; D003593:Cytoplasm; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology; D019076:Transgenes; D019061:src-Family Kinases / Q000502:physiology*
D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases