Hyperinducibility of HLA class II expression of thyroid follicular cells from Graves' disease. A primary defect?
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Hyperinducibility of HLA class II expression of thyroid follicular cells from Graves' disease. A primary defect? / Sospedra, M; Obiols, G; Babi, L F; Tolosa, E; Vargas, F; Roura-Mir, C; Lucas-Martin, A; Ercilla, G; Pujol-Borrell, R.
In: J IMMUNOL, Vol. 154, No. 8, 15.04.1995, p. 4213-22.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Hyperinducibility of HLA class II expression of thyroid follicular cells from Graves' disease. A primary defect?
AU - Sospedra, M
AU - Obiols, G
AU - Babi, L F
AU - Tolosa, E
AU - Vargas, F
AU - Roura-Mir, C
AU - Lucas-Martin, A
AU - Ercilla, G
AU - Pujol-Borrell, R
PY - 1995/4/15
Y1 - 1995/4/15
N2 - Thyroid follicular cells (thyrocytes) from Graves' disease (GD) patients' thyroid glands express HLA class II molecules "ectopically." This phenomenon has been attributed to induction by locally produced cytokines and may be relevant to disease pathogenesis. We have compared IFN-gamma-mediated induction of HLA class II in thyrocytes from glands affected with GD and a nonautoimmune disease (MNG), to investigate a possible differential regulation of HLA expression between these two pathologies. HLA induction has been measured in primary thyrocyte cultures and control autologous macrophages stimulated or not stimulated with IFN-gamma. Comparison of flow cytometric data using an improved algorithm demonstrated that expression of HLA class II molecules is more readily induced in thyrocytes from GD than from MNG thyroid glands. This higher inducibility was parallel to a faster and stronger induction of HLA class II message in GD thyrocytes but did not correlate with the levels of HLA class II or class I originally expressed by thyrocytes in the tissue or with the degree of lymphocytic infiltration of the gland. There was no association with a particular HLA class II allele or with the presence of IFN-gamma and IL-2 in the tissue, as assessed by reverse transcription-PCR. No differences in the induction of class II were found in macrophages from each group of patients. These results suggest that an intrinsic feature of thyrocytes from GD patients is an up-regulation of HLA class II expression and that this is a characteristic that may facilitate the triggering of autoimmunity to "hyperinducible" thyroid glands.
AB - Thyroid follicular cells (thyrocytes) from Graves' disease (GD) patients' thyroid glands express HLA class II molecules "ectopically." This phenomenon has been attributed to induction by locally produced cytokines and may be relevant to disease pathogenesis. We have compared IFN-gamma-mediated induction of HLA class II in thyrocytes from glands affected with GD and a nonautoimmune disease (MNG), to investigate a possible differential regulation of HLA expression between these two pathologies. HLA induction has been measured in primary thyrocyte cultures and control autologous macrophages stimulated or not stimulated with IFN-gamma. Comparison of flow cytometric data using an improved algorithm demonstrated that expression of HLA class II molecules is more readily induced in thyrocytes from GD than from MNG thyroid glands. This higher inducibility was parallel to a faster and stronger induction of HLA class II message in GD thyrocytes but did not correlate with the levels of HLA class II or class I originally expressed by thyrocytes in the tissue or with the degree of lymphocytic infiltration of the gland. There was no association with a particular HLA class II allele or with the presence of IFN-gamma and IL-2 in the tissue, as assessed by reverse transcription-PCR. No differences in the induction of class II were found in macrophages from each group of patients. These results suggest that an intrinsic feature of thyrocytes from GD patients is an up-regulation of HLA class II expression and that this is a characteristic that may facilitate the triggering of autoimmunity to "hyperinducible" thyroid glands.
KW - Adolescent
KW - Adult
KW - Aged
KW - Base Sequence
KW - Child
KW - DNA Primers
KW - Female
KW - Gene Expression
KW - Genes, MHC Class II
KW - Goiter, Nodular
KW - Graves Disease
KW - HLA-D Antigens
KW - Haplotypes
KW - Humans
KW - Interferon-gamma
KW - Macrophages
KW - Male
KW - Middle Aged
KW - Molecular Sequence Data
KW - RNA, Messenger
KW - Thyroid Gland
M3 - SCORING: Journal article
C2 - 7706756
VL - 154
SP - 4213
EP - 4222
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 8
ER -