Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity: a contributing factor to the breach of tolerance to thyroid antigens?
According to the 'aberrant HLA expression' hypothesis, endocrine autoimmunity is driven by presentation of self antigens by target cells over-expressing HLA molecules. In autoimmune thyroid diseases (AITD), thyroid follicular cells (thyrocytes) over-express HLA class I and HLA class II molecules. Since efficient presentation of endogenous peptides via class I requires transporters that translocate endogenous peptides from the cytoplasm to the endoplasmic reticulum, i.e. transporters associated with antigen processing (TAP) -1 and -2, the capability of thyrocytes to express TAP and whether TAP is hyperexpressed in AITD glands are issues relevant to the above hypothesis. Results from immunofluorescence and Northern blotting studies on primary thyrocyte cultures and on a thyroid cell line demonstrate that thyrocytes express constitutively TAP-1 at a low level, and that this expression is readily induced by interferon-gamma (IFN-gamma) and to a lesser extent by IFN-alpha. In AITD, but not in non-autoimmune glands, thyrocytes hyperexpress TAP-1, as demonstrated by both immunohistopathology and flow cytometry. The cytokine pattern does not bear, as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), a clear relationship with TAP-1 expression. These results have broad implications and suggest that the core concept of the 'aberrant HLA expression' hypothesis of endocrine autoimmunity could be incorporated in the currently prevailing view of 'autoimmunity by breach of peripheral tolerance'.
Sospedra
M
M
Immunology Division, University Hospital Germans Trias i Pujol, Badalona, Spain.
Tolosa
E
E
Armengol
P
P
Ashhab
Y
Y
Urlinger
S
S
Lucas-Martin
A
A
Foz-Sala
M
M
Jaraquemada
D
D
Pujol-Borrell
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013961:Thyroid Gland / Q000276:immunology* / Q000378:metabolism*
D001323:Autoantibodies; D002352:Carrier Proteins; D016207:Cytokines; D006680:HLA Antigens; D016898:Interferon-alpha; D012333:RNA, Messenger; D007371:Interferon-gamma