CD4 + CD25 + FOXP3 + regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses

Activation of self-reactive T cells in healthy adults is prevented by the presence of autoantigen-specific CD4 + CD25 + regulatory T cells (CD25 + T r e g ). To explore the functional development of autoantigen-reactive CD25 + T r e g in humans we investigated if thymic CD25 + T r e g from children aged 2 months to 11 years and cord blood CD25 + T r e g are able to suppress proliferation and cytokine production induced by specific antigens. While CD4 + CD25 - thymocytes proliferated in response to myelin oligodendrocyte glycoprotein (MOG), tetanus toxoid and beta-lactoglobulin, suppression of proliferation was not detected after the addition of thymic CD25 + T r e g . However, CD25 + T r e g inhibited interferon (IFN)-y production induced by MOG, which indicates that MOG-reactive CD25 + T r e g are present in the thymus. In contrast, cord blood CD25 + T r e g suppressed both proliferation and cytokine production induced by MOG. Both cord blood and thymic CD25 + T r e g expressed FOXP3 mRNA. However, FOXP3 expression was lower in cord blood than in thymic CD25 + T cells. Further characterization of cord blood CD25 + T cells revealed that FOXP3 was highly expressed by CD25 + CD45RA + cells while CD25 + CD45RA - cells contained twofold less FOXP3, which may explain the lower expression level of FOXP3 in cord blood CD25 + T cells compared to thymic CD25 + T cells. In conclusion, our data demonstrate that low numbers of MOG-reactive functional CD25 + T r e g are present in normal thymus, but that the suppressive ability of the cells is broader in cord blood. This suggests that the CD25 + T r e g may be further matured in the periphery after being exported from the thymus.