Induction of interleukin-2 unresponsiveness and down-regulation of the JAK-STAT system upon activation through the T cell receptor.
Full activation of T cells with antigen (Ag) and antigen-presenting cells initiates effector functions and proliferation. When T cells are re-stimulated through the T cell receptor (TCR) after a primary stimulation with Ag, growth arrest and cell death are induced. Activation of a T cell clone by cross-linking of TCR induces interleukin (IL)-2 unresponsiveness and ultimately cell death. While the proliferative signal delivered by IL-2 induces c-myc, bcl-2 and cyclin D3 expression, the expression of bcl-2 and cyclin D3 is completely suppressed upon TCR stimulation. Furthermore, TCR stimulation induces a decrease in the protein levels of JAK3 and STAT5, suggesting that IL-2 unresponsiveness and growth arrest of T cells result from down-regulation of JAK3 and STAT5.
Miyatake
S
S
Division of Molecular Genetics, Chiba University School of Medicine, Japan.
Sakuma
M
M
Saito
T
T
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000502:physiology*; D053616:Janus Kinase 3; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008894:Milk Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D015534:Trans-Activators / Q000378:metabolism*
C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008894:Milk Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3