Hyperinducibility of HLA class II expression of thyroid follicular cells from Graves' disease. A primary defect?
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.
Sospedra
M
M
Immunology Unit, University Hospital Germans Trias i Pujol, Badalona, Spain.
Obiols
G
G
Babi
L F
LF
Tolosa
E
E
Vargas
F
F
Roura-Mir
C
C
Lucas-Martin
A
A
Ercilla
G
G
Pujol-Borrell
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D005802:Genes, MHC Class II; D006044:Goiter, Nodular / Q000276:immunology*; D006111:Graves Disease / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D013961:Thyroid Gland / Q000276:immunology*
D017931:DNA Primers; D006681:HLA-D Antigens; D012333:RNA, Messenger; D007371:Interferon-gamma