title: CD4+ T cell hyper-responsiveness in CD45 transgenic mice is independent of isoform.
abstract: 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.
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK. rsalmond@staffmail.ed.ac.uk
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Salmond
authors.forename: Louise
authors.initials: L
authors.lastname: McNeill
authors.forename: Nick
authors.initials: N
authors.lastname: Holmes
authors.forename: Denis R
authors.initials: DR
authors.lastname: Alexander
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002452:Cell Count; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D017493:Leukocyte Common Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D020033:Protein Isoforms; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases