Abrogation of CD30 and OX40 signals prevents autoimmune disease in FoxP3-deficient mice

Fabrina Gaspal, David Withers, M Saini, V Bekiaris, Fiona McConnell, Andrea White, Mahmood Khan, H Yagita, Lucy Walker, Graham Anderson, Peter Lane

Research output: Contribution to journalArticle

43 Citations (Scopus)


Our previous studies have implicated signaling through the tumor necrosis family receptors OX40 and CD30 as critical for maintaining CD4 memory responses. We show that signals through both molecules are also required for CD4 effector-mediated autoimmune tissue damage. Under normal circumstances, male mice deficient in the forkhead transcription factor FoxP3, which lack regulatory CD4 T cells, develop lethal autoimmune disease in the first few weeks of life. However, in the combined absence of OX40 and CD30, FoxP3-deficient mice develop normally and breed successfully. The extensive tissue infiltration and organ destruction characteristic of FoxP3 disease does not appear in these mice, and their mortality is not associated with autoimmunity. Although the absence of OX40 plays the dominant role, FoxP3-deficient mice sufficient in CD30 but deficient in OX40 signals still eventually develop lethal disease. This result was supported by the observation that blocking antibodies to OX40 and CD30 ligands also abrogated disease mediated by FoxP3-deficient T cells. These observations identify OX40 and CD30 signals as essential for the development of clinically relevant CD4-dependent autoimmunity and suggest that combination therapies that abrogate these signals might be used to treat established human autoimmune diseases.
Original languageEnglish
Pages (from-to)1579-1584
Number of pages6
JournalThe Journal of Experimental Medicine
Issue number8
Publication statusPublished - 1 Aug 2011


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