Induction of diabetes in NOD‹–›C57BL/6 embryo aggregation chimeras by cyclophosphamide through preferential depletion of C57BL/6 lymphocytes

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

The majority of embryo aggregation (EA) mouse chimeras between non-obese diabetic (NOD) mice and C57BL/6 (B6) mice show clear signs of insulitis frequently accompanied by beta-cell destruction. Less than 5% of these chimeras, however, spontaneously progress to autoimmune diabetes, an incidence far lower than observed in NOD mice. The resistance in chimeras can be accounted for by the target organ chimerism and/or the immune system chimerism. To investigate the mechanism(s) controlling diabetes resistance in these mice, we studied a total of 92 NOD<-->B6 EA chimeras that showed overt lymphoid chimerism and treated 34 chimeras with cyclophosphamide (CY), a compound known to precipitate an acute form of insulin-dependent diabetes mellitus (IDDM) in pre-diabetic NOD mice, by interfering with regulatory mechanisms. We found that CY-treated EA chimeras displayed an increase in the NOD:B6 lymphocyte ratio and 32% of them developed diabetes that could be adoptively transferred to irradiated NOD or NOD-rag-2-/- mice. These findings suggest that lymphocyte chimerism rather than beta-cell chimerism accounts for diabetes resistance in NOD<-->B6 EA chimeras and that the susceptibility to CY-induced diabetes may be related to the proportion of NOD versus B6 lymphoid cells.

Lejon, Kristina,1967-Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Cell and Molecular Biology. University of Umeå(Swepub:umu)krle0001 (author)
Cilio, Corrado M.Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Paediatrics, University of Rome ‘La Sapienza’ Rome, Italy,Department for Cell and Molecular Biology, University of Umeå, Umeå, Sweden (author)
Bergqvist, IngelaUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department for Cell and Molecular Biology, University of Umeå, Umeå, Sweden (author)
Matsunaga, TakeshiUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department for Cell and Molecular Biology, University of Umeå, Umeå, Sweden (author)
Holmberg, Dan,1954-Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Cell and Molecular Biology. University of Umeå(Swepub:umu)daho0001 (author)
Umeå universitetInstitutionen för molekylärbiologi (Medicinska fakulteten) (creator_code:org_t)

By the author/editor: Colucci, Frances ...; Lejon, Kristina, ...; Cilio, Corrado M ...; Bergqvist, Ingel ...; Matsunaga, Takes ...; Holmberg, Dan, 1 ...

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