title: 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.
authors.affiliation: Pediatric Department, University of Insubria c/o Filippo Del Ponte Hospital General Pathology and Immunology Laboratory, University of Insubria, Varese, Italy.
authors.forename: F P
authors.initials: FP
authors.lastname: Pellegrini
authors.forename: M
authors.initials: M
authors.lastname: Marinoni
authors.forename: V
authors.initials: V
authors.lastname: Frangione
authors.forename: A
authors.initials: A
authors.lastname: Tedeschi
authors.forename: V
authors.initials: V
authors.lastname: Gandini
authors.forename: F
authors.initials: F
authors.lastname: Ciglia
authors.forename: L
authors.initials: L
authors.lastname: Mortara
authors.forename: R S
authors.initials: RS
authors.lastname: Accolla
authors.forename: L
authors.initials: L
authors.lastname: Nespoli
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics*; D002478:Cells, Cultured / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D004314:Down Syndrome / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D020022:Genetic Predisposition to Disease; D050031:Hashimoto Disease / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007223:Infant; D018655:Lymphocyte Count; D008297:Male; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors