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International Immunology, Vol. 15, No. 11, pp. 1309-1317, November 2003
© 2003 Japanese Society for Immunology

Differential activation of signal transducer and activator of transcription (STAT)3 and STAT5 and induction of suppressors of cytokine signalling in Th1 and Th2 cells

Per Anderson1,2, Anette Sundstedt4,5, Li Li1,2, Emma J. O’Neill4,6, Suling Li2,3, David C. Wraith4 and Ping Wang1,2

1 Institute of Cell and Molecular Sciences, Barts and The London School of Medicine and Dentistry, London EC1A 7ED, UK 2 Tumor Immunology, Lund University, 22184 Lund, Sweden 3 Department of Biological sciences, Brunel University, Uxbridge UB8 3PH, UK 4 Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol BS8 1TD, Bristol, UK 5 Present address: Active Biotech Research, PO Box 724, 22007 Lund, Sweden 6 Present address: Department of Small Animal Clinical Studies, Veterinary College, University College Dublin, Dublin 4, Ireland

These first two authors contributed equally to this work
Correspondence to: P. Anderson, Institute of Cell and Molecular Sciences, Barts and The London School of Medicine and Dentistry, 59 Bartholomew’s Close, London EC1A 7ED, UK. E-mail: Per.Anderson{at}wblab.lu.se
Transmitting editor: E. Simpson

Cytokines direct the differentiation of naive CD4+ T cells into either IFN-{gamma}-producing Th1 cells or IL-4-producing Th2 cells. In this study, we analyzed the activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT5 (together with STAT4 and STAT6), and the expression of the recently identified suppressor of cytokine signalling (SOCS) proteins, in differentiated Th1 and Th2 cells, both before and after re-stimulation with anti-CD3 and anti-CD28. In addition to the polarized activation of STAT4 in Th1 cells and STAT6 in Th2 cells, we found that STAT3 and STAT5 are selectively activated in Th1 cells after differentiation. This activation of STAT3 and STAT5 was maintained after TCR re-stimulation. The selective activation of STAT3 and STAT5 in Th1 cells was associated with differential induction of SOCS molecules. After re-stimulation, SOCS1 expression was significantly increased in Th2 cells, but not in Th1 and non-polarized ‘Th’ cells. Additionally, the level of CIS was higher in Th2 cells compared with Th1 and Th cells. In contrast, the expression of SOCS3 was higher in Th1 cells. The differential induction of SOCS proteins was paralleled by the differential expression of cytokines in re-stimulated Th1 and Th2 cells (IFN-{gamma} and IL-4/IL-13 respectively). Our results suggests that STAT3 and STAT5, possibly regulated by the SOCS proteins, may play a role in the differentiation of Th cells, and in the maintenance of the Th1 and Th2 phenotype.

Keywords: signal transducer and activator of transcription, suppressor of cytokine signalling, Th


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