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  Different role of Apaf-1 in positive selection, negative selection and death by neglect in foetal thymic organ culture

Matsuki, Y., Zhang, H. G., Hsu, H. C., Yang, P. A., Zhou, T., Dodd, C. H., et al. (2002). Different role of Apaf-1 in positive selection, negative selection and death by neglect in foetal thymic organ culture. Scandinavian Journal of Immunology, 56(2), 174-184. Retrieved from http://onlinelibrary.wiley.com/doi/10.1046/j.1365-3083.2002.01120.x/pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-F345-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-E42F-2
Genre: Journal Article

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 Creators:
Matsuki, Y., Author
Zhang, H. G., Author
Hsu, H. C., Author
Yang, P. A., Author
Zhou, T., Author
Dodd, C. H., Author
Cecconi, F., Author
Gruss, P.1, Author              
Tadakuma, T., Author
Mountz, J. D., Author
Affiliations:
1Department of Molecular Cell Biology, MPI for biophysical chemistry, Max Planck Society, ou_578585              

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 Abstract: Apoptotic protease-activating factor 1 (Apaf-1) is a component of the apoptosome which is required for the activation of procaspase-9. As Apaf-1 knockout (KO) (Apaf-1(-/-)) mice die before birth, the role of Apaf-1 during thymic selection was investigated using 5 day foetal thymic organ culture (FTOC) of thymi obtained at gestational day 15. There was a lower ratio of CD4 single-positive (SP) to CD8 SP cells and decreased apoptosis of CD4(+) CD8(+) (DP) thymocytes from Apaf-1 (-/-) mice compared with wild-type. To determine if these defects resulted in increased production of neglected thymocytes, the Apaf-1 (-/-)mice were crossed with the T-cell receptor (TCR)- alpha-chain KO mice. There was no difference in thymocyte development in the thymi of TCR-alpha (-/-) Apaf-1 (-/-) and TCR-alpha (-/-) Apaf-1 (+/+) mice 5 days after FTOC. To determine if Apaf-1 is involved in apoptosis during death by negative or positive selection, FTOC of the thymus of Apaf-1 D- -/-(b)/HY TCR-alphabeta transgenic (Tg) mice was carried out. There was decreased apoptosis of the HY clonal-specific M33(+) thymocytes and an increased percentage of the autoreactive CD8(+) M33(+) thymocytes in male, but not female Apaf-1 (-/-) D-b/HY TCR Tg mice. Our data suggest that Apaf-1 is not involved in positive selection or death by neglect, but may have a partial role in negative selection during early thymic T-cell development.

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 Dates: 2002-08
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: Scandinavian Journal of Immunology
Source Genre: Journal
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Pages: - Volume / Issue: 56 (2) Sequence Number: - Start / End Page: 174 - 184 Identifier: -