Engagement of T-cell antigen receptor and CD4/CD8 co-receptors induces prolonged STAT activation through autocrine/paracrine stimulation in human primary T cells |
| |
| Authors: | Fu-Yu Chueh Chao-Lan Yu |
| |
| Affiliation: | 3. Research Institute, University Hospital “12 de Octubre,” School of Medicine, Universidad Complutense, Madrid 28041, Spain;4. Institute of Liver Studies, King''s College Hospital, London SE5 9RS, United Kingdom;5. Instituto de Investigaciones Biomédicas Alberto Sols (Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain;1. College of Life Sciences, Liaoning Normal University, Dalian 116081, China;2. Lamprey Research Center, Liaoning Normal University, Dalian 116081, China;1. Department of System Medicine, Pharmacology Section, University of Rome Tor Vergata, Rome, Italy;2. Division of Infection and Immunity, University College London, 5 University Street, London WC1E 6JF, UK;3. Institute of Translational Pharmacology (IFT) National Council of Research Rome, Via Fosso del Cavaliere 100, Rome, Italy;3. Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia;4. Centenary Institute of Cancer Medicine and Cell Biology, New South Wales 2050, Australia;5. Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia;6. Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia;1. Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan;2. Division of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children''s Hospital Medical Center, Cincinnati, OH;3. Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan;4. Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;5. Cancer Science Institute, National University of Singapore, Singapore;6. Harvard Stem Cell Institute, Harvard Medical School, Boston, MA;7. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan |
| |
| Abstract: | Signal transducer and activator of transcription (STAT) proteins are key signaling molecules in response to cytokines and in regulating T cell biology. However, there are contradicting reports on whether STAT is involved in T-cell antigen receptor (TCR) signaling. To better define the role of STAT in TCR signaling, we activated the CD4/CD8-associated Lck kinase by co-crosslinking TCR and CD4/CD8 co-receptors in human peripheral blood T cells. Sequential STAT1, STAT3 and STAT5 activation was observed 1 h after TCR stimulation suggesting that STAT proteins are not the immediate targets in the TCR complex. We further identified interferon-γ as the key cytokine in STAT1 activation upon TCR engagement. In contrast to transient STAT activation in cytokine response, this autocrine/paracrine-induced STAT activation was sustained. It correlated with the absence of two suppressors of cytokine signaling (SOCS) proteins, SOCS3 and cytokine-inducible SH2 containing protein that are negative feedback regulators of STAT signaling. Moreover, enforced expression of SOCS3 inhibited tyrosine phosphorylation of zeta-associated protein kinase of 70 kD in TCR-stimulated human Jurkat T cells. This is the first report demonstrating delayed and prolonged STAT activation coordinated with the loss of SOCS expression in human primary T cells after co-crosslinking of TCR and CD4/CD8 co-receptors. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
