Programmed cell death in the pathogenesis of murine IDDM: resistance to apoptosis induced in lymphocytes by cyclophosphamide

Colucci, FrancescoUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Cell and Molecular Biology, Umeå University, Umeå, Sweden (författare)

Programmed cell death in the pathogenesis of murine IDDM : resistance to apoptosis induced in lymphocytes by cyclophosphamide

The non-obese diabetic (NOD) mouse displays several immune related defects, each of which could potentially contribute to the immunopathogenesis of diabetes that spontaneously develops in these mice. The reported resistance of NOD-lymphocytes to several apoptosis-inducing signals constitutes one such factor. Apoptosis plays a key role in the homeostasis of the immune system, as a means of selecting lymphocyte repertoires both in primary lymphoid organs and in the periphery; distortions in the apoptotic machinery may therefore be hypothesized to be implicated in the pathogenesis of autoimmune disorders. We now report that cyclophosphamide constitutes an apoptosis signal to peripheral lymphocytes and we provide evidence that NOD B cells as well as both CD4 and CD8 T cells display resistance to cyclophosphamide-induced apoptosis. These observations support the notion that apoptosis resistance in NOD mice exists at various levels, and suggest that the CY-sensitive lymphoid population, believed to play an important role in inhibiting the disease in diabetes resistant NOD mice (particularly males), may be controlled by mechanisms that are mediated by apoptosis.

Cilio, Corrado M.Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Pediatrics, University of Rome ‘La Sapienza’ Rome, Italy,Department of Cell and Molecular Biology, Umeå University, Umeå, Sweden (författare)
Lejon, Kristina,1967-Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Cell and Molecular Biology. University of Umeå(Swepub:umu)krle0001 (författare)
Penha Gonçalves, CarlosUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Cell and Molecular Biology. University of Umeå (författare)
Bergman, Marie-LouiseUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Cell and Molecular Biology. University of Umeå (författare)
Holmberg, Dan,1954-Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Cell and Molecular Biology. University of Umeå(Swepub:umu)daho0001 (författare)
Umeå universitetInstitutionen för molekylärbiologi (Medicinska fakulteten) (creator_code:org_t)

Av författaren/redakt...: Colucci, Frances ...; Cilio, Corrado M ...; Lejon, Kristina, ...; Penha Gonçalves, ...; Bergman, Marie-L ...; Holmberg, Dan, 1 ...

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