CD8 Blockade Promotes Antigen Responsiveness to Nontolerizing Antigen in Tolerant Mice by Inhibiting Apoptosis of CD4 super(+) T Cells

• Published in: Journal of Immunology 2007-05, Vol.178 (10), p.6148-6157
• Main Authors: Wang, Zhuangzhi, Davies, Joanna D
• Format: Article
• Language: English
• ISSN: 0022-1767; 1365-2567

Using the DO11.10 CD4 super(+) TCR-transgenic mouse system, we have recently shown that CD8 blockade promotes the expansion of Ag-specific regulatory CD4 super(+) T cells in mice made tolerant to OVA with anti-CD4 mAb. We now show that CD8 blockade is also critical to promoting responses to nontolerizing Ag in anti-CD4 mAb-treated tolerant mice. Previously published work shows that treatment with anti-CD4 mAb without CD8 blockade induces Ag-specific tolerance. We now show that, in addition to inducing tolerance, anti-CD4 mAb treatment also significantly reduces responsiveness to irrelevant, nontolerizing Ag, and this unresponsiveness is associated with significant apoptosis of the CD4 super(+) T cells. Anti-CD4 mAb-induced apoptosis is inhibited by cotreatment with anti-CD8 mAb and responsiveness to irrelevant Ag is restored, while Ag-specific tolerance is maintained. These data suggest that CD8 blockade promotes responsiveness to nontolerizing Ags in tolerant mice by inhibiting CD4 super(+) T cell apoptosis.