| Título: | Insights into the mechanism of CD45-mediated apoptosis in lymphocytes, and establishment of related flow cytometric assays for the detection of cell surface antigens and apoptotic cells |
| Autores: | Fortin, Marylene. |
| Fecha: | 2002 |
| Publicador: | McGill University - MCGILL |
| Fuente: |
 |
| Tipo: | Electronic Thesis or Dissertation |
| Tema: | Health Sciences, Immunology. |
| Descripción: | The CD45 protein tyrosine phosphatase (PTP) is a large transmembrane glycoprotein abundantly expressed on all nucleated cells of the hematopoietic system. CD45 plays an essential role in signal transduction through the antigen receptor in T and B lymphocytes, mainly through the regulation of Src-family tyrosine kinase activity. Previous work has shown that cross-linking CD45 with monoclonal antibodies can induce caspase-independent apoptosis in murine immature T cells. The exact mechanism whereby CD45 cross-linking can lead to cell death, and whether the PTP activity of CD45 is involved in this process have not been determined. In this study, a CD45-deficient T-cell line was transduced with either wild-type or phosphatase-dead CD45 retroviral constructs, to show that the PTP activity of CD45 was totally dispensable for apoptosis triggering after cross-linking of the molecule. Noteworthy, a T-cell line expressing a truncated form of CD45, lacking most of the cytoplasmic domain, could readily be killed by CD45 cross-linking. It was also demonstrated that LPAP, a protein of undefined function interacting specifically with the transmembrane domain of CD45, does not play an essential role in CD45-triggered apoptosis. Taken together, these results suggest that the extracellular and/or transmembrane domains of CD45 are endowed with unique properties in apoptosis signaling. To our knowledge, apoptosis induction is the only function reported to date for CD45 for which PTP activity is not required. Sensitivity towards CD45-mediated cell death had been shown to be modulated during T cell differentiation in the thymus. Hence, a parallel in the susceptibility towards CD45-induced apoptosis was found for the various stages of T and B cell development in primary lymphoid organs. Moreover, it was also demonstrated that mature T-cells from peripheral lymphoid organs readily underwent cell death upon CD45 engagement, whereas peripheral B-cells showed to be resistant to this treatm |
| Idioma: | en |
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