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Temporary, but Essential Requirement of CD8(+) T Cells Early in the Pathogenesis of Diabetes in BB Rats as Revealed by Thymectomy and CD8 Depletion
Autoimmunity-prone BB rats demonstrate a T lymphocytopenia and abnormal T cell subset distribution. To test whether the life span of all T cells or only of certain subsets is reduced in BB rats, we thymectomised 8-week-old BB and PVG rats and subsequently assessed size and composition of the T cell...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2485407/ https://www.ncbi.nlm.nih.gov/pubmed/14768945 http://dx.doi.org/10.1080/10446670310001626508 |
Sumario: | Autoimmunity-prone BB rats demonstrate a T lymphocytopenia and abnormal T cell subset distribution. To test whether the life span of all T cells or only of certain subsets is reduced in BB rats, we thymectomised 8-week-old BB and PVG rats and subsequently assessed size and composition of the T cell population over a 6-week-period. In both strains, thymectomy (Tx) was followed by a decrease in peripheral T cell numbers, which was proportionally larger in BB rats. The decline of the Thy-1(+) recent thymic migrant (RTM) T cell phenotype was similar in both strains. BB rats showed a rapid preferential loss of CD8(+) and CD45RC(+) T cells, whereas the relative loss of RT6(+) T cells was proportional to that of all T cells and not significantly different from that in PVG rats. Tx at 8-week did not prevent diabetes. Tx of 4-week-old BB rats revealed essentially the same changes in peripheral T cell subset distribution as in 8-week-old animals. However, Tx at week 4 did prevent diabetes. Since this raised the possibility of a temporary requirement of CD8(+) T cells for the development of diabetes, we performed CD8 depletions during different pre-diabetic intervals. We found that CD8 depletion from 4 to 8 and 4 to 14 weeks, but not from 8 to 14 weeks of age prevented diabetes. We conclude that the protective effect of early adult Tx is, at least in part, due to the rapid loss of CD8(+) T cells, and that these cells are only required between 4 and 8 weeks of age for diabetes to develop in BB rats. |
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