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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)-a-chain KO mice. There was no difference in thymocyte development in the thymi of TCR-±/± Apaf-1 ±/± and TCR-±/± 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-ab 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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