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 highCD127 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.

Down syndrome, autoimmunity and T regulatory cells

Mortara, L.;Accolla, R.;Nespoli, L.
2012-01-01

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 highCD127 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.
2012
Pellegrini, F. P.; Marinoni, M.; Frangione, V.; Tedeschi, A.; Gandini, V.; Ciglia, F.; Mortara, L.; Accolla, R.; Nespoli, L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/1768897
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