Endocrine Abstracts

Background: Foxp3(+) regulatory T cells (Treg) play a leading role in developing immune tolerance through active suppression in Graves’ disease (GD). The influence of radioactive iodine therapy (RAI) on the differentiated fractions of Treg of GD patients is still poorly understood.

Aim: To estimate the differentiated fractions of blood Tregs and the CD25 expression in patients with GD after RAI.

Materials and Methods: In total, 36 women with recurrent GD (age mean [range]= 46.34±14.32 years [27–59] and 42 age-and sex-matched healthy control subjects were recruited into the study. All patients treated with thiamazole for at 5 months (2 – 9) and withdrawal 14 days before RAI. All patients had a fixed 400-700 MBq radioactive iodine (¹³¹I) dose orally. For the immunophenotyping of Treg differentiating fractions, each whole blood sample (100 µL) was stained using FITC-labeled mouse anti-human CD62l, PE-labeled mouse anti-human CD127, ECD-labeled mouse anti-humanCD45R0, PC5.5-labelled mouse anti-human CD25, PC7-labelled mouse anti-human CD4 (clone T4, cat. 6607101, Beckman Coulter, Indianapolis, IN, USA), A-A700-labelled mouse anti-human CD3 and A-A750-labelled mouse anti-human CD45. The CD25 expression assessed by MFI.

Results: Lower absolute counts of Treg (CD3⁺CD4⁺CD127^LowCD25^High) were found in GD patients before RAI in comparison with healthy controls (P< 0.001). In GD patients up to six month after RAI the absolute and percentage Tregs content was lower relative to initial levels (P< 0.001). In GD patients before and 1, 3 and 6 month after RAI a significant decrease in the percentages of “naïve” (CD45R0⁻CD62L⁺) and terminally differentiated (CD45R0⁻CD62L⁻) Tregs was established relative to the control, and on 3 and 6 months after RAI a significant decrease of this Treg differentiated fractions was observed relative to the values detected in patients before and 1 month after RAI (P< 0.001). Against the background of compensated hypothyroidism in GD patients on 3 and 6 months after RAI we observed a significant decrease than in healthy individuals in expression of MFI CD25 on “naïve” and terminally differentiated Tregs (P< 0.001), and сentral memory Tregs (CD45R0⁺ CD62L⁺) (P< 0.001).

Conclusion: There is expanding knowledge on new Treg imbalance that is crucial for the development of GD. The role and importance of “naïve” and terminally differentiated Treg in the pathogenesis of GD allows not only a better understanding of the mechanisms of development and reccurence of these diseases, but also helps to define immunotherapy targets that can be restored by increasing the number and function of Tregs.