International Immunology Advance Access originally published online on April 30, 2008
International Immunology 2008 20(7):819-827; doi:10.1093/intimm/dxn040
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CD4+ T cell hyper-responsiveness in CD45 transgenic mice is independent of isoform
1 Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK
2 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
3 Present address: Institute of Immunology and Infection Research, Ashworth Laboratories, King's Buildings, West Mains Road, Edinburgh, EH9 3JT, UK
Correspondence to: R.J. Salmond, Institute of Immunology and Infection Research, Ashworth Laboratories, King's Buildings, West Mains Road, Edinburgh, EH9 3JT, UK. E-mail: rsalmond{at}staffmail.ed.ac.uk
The CD45 tyrosine phosphatase is required for T cell development and function by virtue of its role as a positive regulator of src family kinase activity. In addition, recent data have highlighted that CD45 also acts as a negative regulator of Lck function by dephosphorylation of critical tyrosine residues. Lck functionality and TCR responsiveness are elevated in transgenic mice expressing the CD45RO isoform at ‘intermediate’ (10–40% of wild type) levels, indicating that the expression level of CD45 is critical in determining the sensitivity of T cells to TCR stimulation. However, it is unclear whether such a phenotype is specific for the CD45RO isoform, typically expressed by activated T cells. In the present work, the roles of three isoforms of CD45, RO, RB and RABC, in thymocyte development, T cell responses and TCR signalling pathways were directly compared. The data demonstrate that expression of CD45RB or CD45RABC at intermediate levels also results in CD4+ T cell hyper-reactivity, as previously published for CD45RO. These data emphasize the dual functions of CD45 as both a positive and a negative regulators of TCR signalling irrespective of specific isoform expression.
Keywords: cell activation, signal transduction, T lymphocyte
* These authors contributed equally to this work.
Transmitting editor: D. Fearon
Received 8 January 2008, accepted 2 April 2008.
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