Abundant CD4+FOXP3+ regulatory T cells fail to suppress the proliferation of T cells in patients with Turner syndrome

Context

Why Turner syndrome (TS) patients are predisposed to autoimmune disease remains unclear.

Objective

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.

Methods

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⁺CD25^bright were co-cultured with autologous CD4⁺CD25⁻ target cells in the presence of anti-CD3 and CD28 antibodies to assess their suppressive function.

Results

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).

Conclusions

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.