| First Author | Dubois B | Year | 2003 |
| Journal | Blood | Volume | 102 |
| Issue | 9 | Pages | 3295-301 |
| PubMed ID | 12855551 | Mgi Jnum | J:115675 |
| Mgi Id | MGI:3692062 | Doi | 10.1182/blood-2003-03-0727 |
| Citation | Dubois B, et al. (2003) Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation. Blood 102(9):3295-301 |
| abstractText | To elucidate the role of CD4+CD25+ regulatory T cells in oral tolerance, we used the model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB), which is mediated by CD8+ Tc1 effector cells independently of CD4+ T-cell help. Conversely to normal mice, invariant chain knock-out (KO) (Ii degrees / degrees ) mice, which are deficient in CD4+ T cells, cannot be orally tolerized and develop a chronic hapten-specific CHS response. Transfer of naive CD4+ T cells before hapten gavage into Ii degrees / degrees mice restores oral tolerance by a mechanism independent of interleukin-10 (IL-10) production by CD4+ T cells. That naturally occurring CD4+CD25+ T cells are critical for oral tolerance induction is demonstrated by the finding that (1) transfer of CD4+CD25+ but not CD4+CD25- T cells into Ii degrees / degrees recipients completely prevents the CHS response and skin infiltration by CD8+ T cells, by blocking development of hapten-specific CD8+ T cells; (2) in vivo depletion of CD4+CD25+ cells by antibody treatment in normal mice impairs oral tolerance; and (3) CD4+CD25+ T cells inhibit hapten-specific CD8+ T-cell proliferation and interferon gamma (IFN gamma) production, in vitro. These data show that naturally occurring CD4+CD25+ T cells are instrumental for orally induced tolerance and are key actors for the control of antigen-specific CD8+ T-cell effectors mediating skin inflammation. |
