Down syndrome, autoimmunity and T regulatory cells.

Abstract

Autoimmune diseases are more represented in Down syndrome (DS) individuals compared to chromosomally normal people. Natural T regulatory cells (nT(reg) ) have been considered to be primary in the role of controlling the intensity and targets of the immune response. We have investigated the phenotypical and functional alteration of nT(reg) in a group of DS people. The phenotypical characteristic of T(reg) cells of 29 DS was analysed and compared with an age-matched healthy control group. The inhibitory potential of CD4(+) CD25(high) CD127(low) T regulatory cells was evaluated on autologous CD4(+) CD25(-) T cell proliferation in response to activation with a mytogenic pan-stimulus (anti-CD2, anti-CD3 and anti-CD28 antibodies). The CD4(+) CD25(high) cells in the DS and control groups were 2·692±0·3808%, n=29 and 1·246±0·119, n=29%, respectively (P=0.0007), with a percentage of forkhead box protein 3 (FoxP3)-expressing cells of 79·21±3·376%, n=29 and 59·75±4·496%, respectively (P=0.0015). CD4(+) CD25(+) FoxP3(+) cells were increased in peripheral blood from DS subjects (DS mean 5·231±0·6065% n=29, control mean 3·076±0·3140% n=29). The majority of CD4(+) CD25(high) were CD127(low) and expressed a high percentage of FoxP3 (natural T(reg) phenotype). While the proliferative capacity of DS T cells was not altered significantly compared to normal individuals, a reduced inhibitory potential of T(reg) compared to healthy controls was clearly observed (mean healthy control inhibition in T(eff) : T(reg) 1:1 co-culture: 58·9%±4·157%, n=10 versus mean DS inhibition in T(eff) :T(reg) 1:1 co-culture: 39·8±4·788%, n=10, P=0.0075; mean healthy control inhibition in T(eff) : T(reg) 1:0·5 co-culture: 45·10±5·858%, n=10 versus DS inhibition in T(eff) : T(reg) 1:0·5 co-culture: 24·10±5·517%, n=10, P=0.0177). DS people present an over-expressed peripheral nT(reg) population with a defective inhibitory activity that may partially explain the increased frequency of autoimmune disease.