Cutting edge: TCR stimulation by antibody and bacterial superantigen induces Stat3 activation in human T cells.
Recent data show that TCR/CD3 stimulation induces activation of Stat5 in murine T cells. Here, we show that CD3 ligation by mAb and Staphylococcal enterotoxin (SE) induce a rapid, gradually accumulating, long-lasting tyrosine, and serine phosphorylation of Stat3 (but not Stat5) in allogen-specific human CD4+ T cell lines. In contrast, IL-2 induces a rapid and transient tyrosine and serine phosphorylation of Stat3. Compared with IL-2, CD3 ligation induces a delayed Stat3 binding to oligonucleotide probes from the ICAM-1 and IL-2R alpha promoter. CD3-mediated activation of Stat3 is almost completely inhibited by a Src kinase inhibitor (PP1), whereas IL-2-induced Stat3 activation is unaffected. In conclusion, we show that CD3 ligation by mAb and SE triggers a rapid, PP1-sensitive tyrosine and serine phosphorylation of Stat3 in human CD4+ T cells. Moreover, we provide evidence that TCR/CD3 and IL-2 induce Stat3 activation via distinct signaling pathways.
Gerwien
J
J
Institute of Medical Microbiology and Immunology, Institute for Medical Anatomy, University of Copenhagen, Denmark.
Nielsen
M
M
Labuda
T
T
Nissen
M H
MH
Svejgaard
A
A
Geisler
C
C
Röpke
C
C
Odum
N
N
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D009841:Oligonucleotides / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000502:physiology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D009841:Oligonucleotides; D011948:Receptors, Antigen, T-Cell; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018089:Superantigens; D015534:Trans-Activators; C026066:enterotoxin A, Staphylococcal; D014443:Tyrosine; D004247:DNA