BACKGROUND: The role of costimulatory molecules expressed on lymphocytes and thyrocytes in hyperthyroidism has attracted increasing attention and research has shown a close correlation between variant expression of these molecules on lymphocytes and thyrocytes and the development of GD. MATERIALS AND METHODS: [corrected] Thyroid tissues were collected from GD patients during surgery and from Hashimoto disease (HT) and non-toxic goiter (NTG) patients as controls. ICOSL expression on infiltrated B cells and TFC was detected by flow cytometry (FCM), reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Variation in ICOSL expression on TFC in primary cultures was analyzed in the absence or presence of cytokines using FCM assays. The role of ICOS-ICOSL signaling in proliferation, thyroid hormone production and thyroglobulin (Tg) release was investigated in primary TFC cultures using ICOS gene transfected L929 cells (ICOS-L929 cells) and the blocking ICOSL antibody (11 C4) in MTT assays and radioimmunoassays. RESULTS AND DISCUSSION: ICOSL expression on infiltrated B cells and TFC was detected in GD patient tissue. However, ICOSL expression was only detected on infiltrated B cells in control HT and NTG patient tissue. ICOSL expression on TFC was induced in vitro by the proinflammatory cytokines IFN-γ, IL-6 and TNF-α. Compared with mock transfected L929 (mock-L929) control cells, ICOS-L929 cells promoted significant proliferation of primary cultured TFC, with increased thyroid hormone and Tg production (all P < 0.01). TFC proliferation and production of thyroid hormones and Tg were inhibited significantly in the presence of ICOSL blocking antibody (11 C4) (all P < 0.05). Our observations suggest that ICOS-ICOSL signal plays a direct role in proliferation and differentiation of TFC and may exert important effects in the initiation, maintenance and exaggeration of autoimmune responses in local tissue.
BACKGROUND: The role of costimulatory molecules expressed on lymphocytes and thyrocytes in hyperthyroidism has attracted increasing attention and research has shown a close correlation between variant expression of these molecules on lymphocytes and thyrocytes and the development of GD. MATERIALS AND METHODS: [corrected] Thyroid tissues were collected from GDpatients during surgery and from Hashimoto disease (HT) and non-toxic goiter (NTG) patients as controls. ICOSL expression on infiltrated B cells and TFC was detected by flow cytometry (FCM), reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Variation in ICOSL expression on TFC in primary cultures was analyzed in the absence or presence of cytokines using FCM assays. The role of ICOS-ICOSL signaling in proliferation, thyroid hormone production and thyroglobulin (Tg) release was investigated in primary TFC cultures using ICOS gene transfected L929 cells (ICOS-L929 cells) and the blocking ICOSL antibody (11 C4) in MTT assays and radioimmunoassays. RESULTS AND DISCUSSION: ICOSL expression on infiltrated B cells and TFC was detected in GDpatient tissue. However, ICOSL expression was only detected on infiltrated B cells in control HT and NTG patient tissue. ICOSL expression on TFC was induced in vitro by the proinflammatory cytokines IFN-γ, IL-6 and TNF-α. Compared with mock transfected L929 (mock-L929) control cells, ICOS-L929 cells promoted significant proliferation of primary cultured TFC, with increased thyroid hormone and Tg production (all P < 0.01). TFC proliferation and production of thyroid hormones and Tg were inhibited significantly in the presence of ICOSL blocking antibody (11 C4) (all P < 0.05). Our observations suggest that ICOS-ICOSL signal plays a direct role in proliferation and differentiation of TFC and may exert important effects in the initiation, maintenance and exaggeration of autoimmune responses in local tissue.
Authors: R A Metcalfe; R S McIntosh; F Marelli-Berg; G Lombardi; R Lechler; A P Weetman Journal: J Clin Endocrinol Metab Date: 1998-04 Impact factor: 5.958
Authors: D Brodie; A V Collins; A Iaboni; J A Fennelly; L M Sparks; X N Xu; P A van der Merwe; S J Davis Journal: Curr Biol Date: 2000-03-23 Impact factor: 10.834
Authors: S K Yoshinaga; M Zhang; J Pistillo; T Horan; S D Khare; K Miner; M Sonnenberg; T Boone; D Brankow; T Dai; J Delaney; H Han; A Hui; T Kohno; R Manoukian; J S Whoriskey; M A Coccia Journal: Int Immunol Date: 2000-10 Impact factor: 4.823
Authors: M Battifora; G Pesce; F Paolieri; N Fiorino; C Giordano; A M Riccio; G Torre; D Olive; M Bagnasco Journal: J Clin Endocrinol Metab Date: 1998-11 Impact factor: 5.958
Authors: Haitao Shen; Na Wu; Gayani Nanayakkara; Hangfei Fu; Qian Yang; William Y Yang; Angus Li; Yu Sun; Charles Drummer Iv; Candice Johnson; Ying Shao; Luqiao Wang; Keman Xu; Wenhui Hu; Marion Chan; Vincent Tam; Eric T Choi; Hong Wang; Xiaofeng Yang Journal: Front Biosci (Landmark Ed) Date: 2019-01-01