Figure 3.

Nasal insufflation enhances Treg function. Anti–MPO CD4⁺ Teffs were cocultured with either CD4⁺Foxp3⁺ or CD4⁺Foxp3⁻ Tregs from upper respiratory tract draining LNs of mice nasally administered with MPO_409–428 at a ratio of 1 Teff to 4 Tregs. (A and B) Both CD4⁺Foxp3⁺ and CD4⁺Foxp3⁻ T cells suppressed anti–MPO Teff cell proliferation compared with OVA_323–339–tolerized CD4⁺ T cells. (C and D) Enhanced Treg function was associated with enhanced IL-10 production from both MPO_409–428–tolerized CD4⁺Foxp3⁺ and CD4⁺Foxp3⁻ T cells. (E–G) Characterization of CD4⁺ T cells from mice nasally insufflated with MPO_409–428 showed a significant increase in ICOS in MPO_409–428–tolerized CD4⁺Foxp3⁺ cells, whereas ICOS, CTLA4, and Folate R4 expressions were all significantly upregulated in MPO_409–428–tolerized CD4⁺Foxp3⁻ cells compared with CD4⁺ T cells from naïve C57BL/6 mice. (H) No difference in expression of GITR was observed between groups. *P<0.05; **P<0.01. CTLA4, cytotoxic T-lymphocyte-associated protein 4; GITR, glucocorticoid-induced tumour-necrosis-factor-receptor; ICOS, inducible T-cell co-stimulator.