TCR signaling thresholds regulating T cell development and activation are dependent upon SHP-1.
An examination of thymocytes and peripheral T cells from SHP-1-deficient motheaten mice possessing a transgenic MHC class I-restricted TCR has implicated SHP-1 in regulating TCR signaling thresholds at three checkpoints in T cell development and activation. First, in the population of CD4-CD8- double negative thymocytes, SHP-1 appears capable of regulating signals from TCR complexes that control the maturation and proliferation of double negative thymocytes. Second, the loss of SHP-1 increased the number of CD4+CD8+ double positive thymocytes capable of maturing as TCRhigh single positive thymocytes. Third, the loss of SHP-1 altered the basal level of activation of naive lymph node T cells. Accordingly, SHP-1-deficient lymph node T cells bearing the transgenic TCR demonstrated a hyperresponsiveness to stimulation with cognate peptide. However, the loss of SHP-1 did not alter the cytolytic ability of mature effector cytotoxic T lymphocytes. Together these results suggest that SHP-1 contributes to establishing thresholds for TCR signaling in thymocytes and naive peripheral T cells.
Johnson
K G
KG
Department of Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
LeRoy
F G
FG
Borysiewicz
L K
LK
Matthews
R J
RJ
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D016516:CD4-CD8 Ratio; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019000:Phosphotyrosine / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*
D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D011948:Receptors, Antigen, T-Cell; D019000:Phosphotyrosine; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse