Abundant CD4+FOXP3+ regulatory T cells fail to suppress the proliferation of T cells in patients with Turner syndrome
© Ah Lee et al; licensee BioMed Central Ltd. 2015
Published: 28 April 2015
Why Turner syndrome (TS) patients are predisposed to autoimmune disease remains unclear.
We investigated whether the frequency, phenotype, and suppressive function of CD4+FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls.
Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4–35.9 yrs) and controls (n = 29) were stained with various Treg markers to characterize their phenotypes. Tregs sorted for CD4+CD25bright were co-cultured with autologous CD4+CD25− target cells in the presence of anti-CD3 and CD28 antibodies to assess their suppressive function.
TS patients exhibited a higher frequency of CD4+FOXP3+ Tregs among their lymphocytes (mean 2.06 vs. 1.52%, P = 0.005) and FOXP3+ Tregs among their CD4+ T cells (7.44 vs. 4.19%, P < 0.001) compared to controls. The expression of inhibitory CTLA-4 in the Tregs of TS patients was also significantly higher (mean fluorescence intensity = 214.1 vs. 184.6, P = 0.003). The frequency of Tregs expressing GITR+, CXCR3+, and CCR4+CCR6+ was comparable between the two groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+CD25− T cells was significantly impaired in TS patients compared to controls (P < 0.05 at a 0.1:1 ratio of Tregs to target cells, P < 0.01 at 0.25:1, 0.5:1, and 1:1).
The Tregs of TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite the abundance of Tregs in the peripheral circulation.
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