Down syndrome, autoimmunity and T regulatory cells

Area of Science:

• Immunology
• Genetics
• Cell Biology

Background:

• Autoimmune diseases are more prevalent in individuals with Down syndrome (DS) than in the general population.
• Natural regulatory T cells (nT(reg)) play a crucial role in maintaining immune homeostasis and preventing autoimmunity.
• Phenotypical and functional characteristics of nT(reg) cells in DS individuals require further investigation.

Purpose of the Study:

• To investigate the phenotypical and functional alterations of nT(reg) cells in individuals with Down syndrome.
• To compare the nT(reg) cell population in DS individuals with age-matched healthy controls.
• To determine if nT(reg) cell dysfunction contributes to the increased autoimmune disease risk in DS.

Main Methods:

• Analysis of phenotypical markers (CD4, CD25, CD127, FoxP3) on T regulatory cells in 29 DS individuals and 29 healthy controls.
• Evaluation of the inhibitory function of CD4(+)CD25(high)CD127(low) T regulatory cells on autologous T cell proliferation.
• Comparison of T cell proliferation and T regulatory cell function between DS and control groups.

Main Results:

• DS individuals exhibited a significantly higher percentage of CD4(+)CD25(high) T cells and CD4(+)CD25(+)FoxP3(+) cells compared to controls.
• The majority of CD4(+)CD25(high) T cells in DS individuals displayed the natural T regulatory cell phenotype (CD127(low), high FoxP3 expression).
• While T cell proliferation was not significantly altered, the inhibitory capacity of nT(reg) cells was markedly reduced in DS individuals compared to healthy controls.

Conclusions:

• Down syndrome individuals present with an over-expressed peripheral nT(reg) cell population.
• These nT(reg) cells exhibit defective inhibitory activity.
• This impaired regulatory function of nT(reg) cells may partially explain the increased frequency of autoimmune diseases observed in the DS population.