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Publication : CD4+ T cell hyper-responsiveness in CD45 transgenic mice is independent of isoform.

First Author  Salmond RJ Year  2008
Journal  Int Immunol Volume  20
Issue  7 Pages  819-27
PubMed ID  18448457 Mgi Jnum  J:136717
Mgi Id  MGI:3796816 Doi  10.1093/intimm/dxn040
Citation  Salmond RJ, et al. (2008) CD4+ T cell hyper-responsiveness in CD45 transgenic mice is independent of isoform. Int Immunol 20(7):819-27
abstractText  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.
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