Document 0998
 DOCN  M9540998
 TI    Entry of CD4-CD8- immature thymocytes into the CD4/CD8 developmental
       pathway is controlled by tyrosine kinase signals that can be provided
       through TCR components.
 DT    9504
 AU    Takahama Y; Hasegawa T; Itohara S; Ball EL; Sheard MA; Hashimoto Y;
       Syntex Institute of Immunology, Ibaraki, Japan.
 SO    Int Immunol. 1994 Oct;6(10):1505-14. Unique Identifier : AIDSLINE
       MED/95127553
 AB    Entry of thymus-migrated precursor cells into the CD4/CD8 developmental
       pathway was analyzed by using the short-term organ cultures of day 14
       fetal mouse thymus lobes. Organ cultures of CD4-CD8- day 14 fetal
       thymocytes for 1-2 days resulted in the generation of CD4-CD8+ cells,
       which were mostly immediate precursor cells for CD4+CD8+ thymocytes.
       This differentiation of CD4-CD8- thymocytes into CD4-CD8+ cells was
       strongly enhanced by anti-CD3 antibodies. The anti-CD3- induced
       generation of CD4-CD8+ cells was even found in the immunodeficient scid
       fetal thymus cultures, and the cell surface CD3 expression on the scid
       fetal thymocytes could be directly visualized, indicating that
       functional CD3 could be expressed on CD4-CD8- immature thymocytes
       without being associated with rearranged TCR components. The
       anti-CD3-induced generation of CD4-CD8+ cells from scid and normal fetal
       thymus cultures was inhibited by tyrosine kinase inhibitors Herbimycin A
       and Tyrphostin. The generation of CD4-CD8+ cells in unstimulated normal
       fetal thymus cultures was also markedly inhibited by the tyrosine kinase
       inhibitors but not by Cyclosporin A, suggesting that tyrosine
       kinase-dependent but calcineurin-independent signals were essential for
       the differentiation of CD4-CD8- thymocytes. Interestingly, the
       generation of CD4-CD8+ cells from the normal fetal thymus cultures was
       modestly but consistently enhanced by anti-TCR beta antibody, suggesting
       that functional TCR beta in addition to CD3 was expressed on normal
       CD4-CD8- immature thymocytes. On the other hand, anti-TCR delta antibody
       did not affect this differentiation in the normal fetal thymus cultures
       and the generation of CD4-CD8+ cells from the fetal thymus cultures of
       TCR delta-deficient mice was still enhanced by anti-TCR beta or anti-CD3
       antibodies, indicating that either TCR delta chains or TCR delta+ cells
       were not involved in the control of the differentiation into CD4-CD8+
       cells. These results indicate that the entry of CD4-CD8- immature
       thymocytes into the CD4/CD8 developmental pathway is controlled by
       tyrosine kinase signals and that these signals can be provided through
       the engagement of TCR-CD3 complexes with or without TCR beta chains
       expressed on the CD4-CD8- immature thymocytes.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY  Cell
       Differentiation/*IMMUNOLOGY  Cells, Cultured  CD4-Positive
       T-Lymphocytes/*PHYSIOLOGY  CD8-Positive T-Lymphocytes/*PHYSIOLOGY  Flow
       Cytometry  Mice  Mice, Inbred C57BL  Mice, Mutant Strains  Mice, SCID
       Organ Culture  Protein-Tyrosine Kinase/*METABOLISM  Receptor-CD3
       Complex, Antigen, T-Cell/PHYSIOLOGY  Receptors, Antigen, T-Cell,
       alpha-beta/*PHYSIOLOGY  Signal Transduction/IMMUNOLOGY  Thymus
       Gland/CYTOLOGY/EMBRYOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).