TY - JOUR
T1 - Regulatory T-cells in Graves' orbitopathy
T2 - Baseline findings and immunomodulation by anti-T lymphocyte globulin
AU - Kahaly, George J.
AU - Shimony, Orly
AU - Gellman, Yechiel N.
AU - Lytton, Simon D.
AU - Eshkar-Sebban, Lora
AU - Rosenblum, Nir
AU - Refaeli, Efrat
AU - Kassem, Sameer
AU - Ilany, Jacob
AU - Naor, David
PY - 2011/2
Y1 - 2011/2
N2 - Background and Aim: Graves' orbitopathy (GO) is characterized by orbital T cell infiltration and local release of proinflammatory cytokines. We aimed to evaluate the involvement of baseline regulatory T (Treg) cells and rabbit anti-T lymphocyte globulin (rATG)-induced Treg cells in GO. Design: Peripheral blood mononuclear cells (PBMCs) from seven patients with Graves' disease (GD) without eye manifestations, 29 patients with GO, and 15 healthy controls were incubated with rATG, washed, and analyzed for expression of Treg cell markers and for ability to suppress mixed lymphocyte reaction. Results: Elevation of CD4 to CD8 ratio and enhanced secretion of IL-6, IL-10, and TNFα were detected in PBMCs of GO patients compared with controls (both P<0.01). Despite this abnormality, the frequencies of CD4+CD25+FoxP3+ of GO and control PBMCs were similar and remained unchanged after 24 h incubation with control rabbit IgG (rIgG). Incubation with polyclonal rATG increased the frequency of PBMCs of GO patients, expressing Treg cell markers (CD25, FoxP3, and the IL-7 receptor CD127low/-) by 2.5-8 fold over corresponding rIgG-incubated cells (P < 0.05). FoxP3/CD4 rATG-induced Treg cell marker expressed more intensively on GO peripheral blood leukocytes (PBLs) than on GD (P < 0.01) or normal (P < 0.05) PBLs, yet its expression on normal PBLs was stronger than on GD PBLs (P < 0.05). GO rATG-incubated PBMCs, but not rIgG-incubated PBMCs, suppressed (P<0.05) proliferation of autologous responder cells stimulated with allogeneic irradiated cells in mixed lymphocyte reaction. Such rATG-induced suppressive activity was not detected in GD. Conclusion: This study is the first to show that PBMCs of patients with GO substantially increase Treg cells in both frequency and potency after in vitro incubation with rATG.
AB - Background and Aim: Graves' orbitopathy (GO) is characterized by orbital T cell infiltration and local release of proinflammatory cytokines. We aimed to evaluate the involvement of baseline regulatory T (Treg) cells and rabbit anti-T lymphocyte globulin (rATG)-induced Treg cells in GO. Design: Peripheral blood mononuclear cells (PBMCs) from seven patients with Graves' disease (GD) without eye manifestations, 29 patients with GO, and 15 healthy controls were incubated with rATG, washed, and analyzed for expression of Treg cell markers and for ability to suppress mixed lymphocyte reaction. Results: Elevation of CD4 to CD8 ratio and enhanced secretion of IL-6, IL-10, and TNFα were detected in PBMCs of GO patients compared with controls (both P<0.01). Despite this abnormality, the frequencies of CD4+CD25+FoxP3+ of GO and control PBMCs were similar and remained unchanged after 24 h incubation with control rabbit IgG (rIgG). Incubation with polyclonal rATG increased the frequency of PBMCs of GO patients, expressing Treg cell markers (CD25, FoxP3, and the IL-7 receptor CD127low/-) by 2.5-8 fold over corresponding rIgG-incubated cells (P < 0.05). FoxP3/CD4 rATG-induced Treg cell marker expressed more intensively on GO peripheral blood leukocytes (PBLs) than on GD (P < 0.01) or normal (P < 0.05) PBLs, yet its expression on normal PBLs was stronger than on GD PBLs (P < 0.05). GO rATG-incubated PBMCs, but not rIgG-incubated PBMCs, suppressed (P<0.05) proliferation of autologous responder cells stimulated with allogeneic irradiated cells in mixed lymphocyte reaction. Such rATG-induced suppressive activity was not detected in GD. Conclusion: This study is the first to show that PBMCs of patients with GO substantially increase Treg cells in both frequency and potency after in vitro incubation with rATG.
UR - http://www.scopus.com/inward/record.url?scp=79951693448&partnerID=8YFLogxK
U2 - 10.1210/jc.2010-1424
DO - 10.1210/jc.2010-1424
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C2 - 21147887
AN - SCOPUS:79951693448
SN - 0021-972X
VL - 96
SP - 422
EP - 429
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -