Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity

TY - JOUR

T1 - Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity

T2 - a contributing factor to the breach of tolerance to thyroid antigens?

AU - Sospedra, M

AU - Tolosa, E

AU - Armengol, P

AU - Ashhab, Y

AU - Urlinger, S

AU - Lucas-Martin, A

AU - Foz-Sala, M

AU - Jaraquemada, D

AU - Pujol-Borrell, R

PY - 1997/7/1

Y1 - 1997/7/1

N2 - 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'.

AB - 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'.

KW - Adolescent

KW - Adult

KW - Aged

KW - Antigen Presentation

KW - Autoantibodies

KW - Autoimmunity

KW - Carrier Proteins

KW - Cells, Cultured

KW - Cytokines

KW - Flow Cytometry

KW - Gene Expression

KW - HLA Antigens

KW - Humans

KW - Immune Tolerance

KW - Immunohistochemistry

KW - Interferon-alpha

KW - Interferon-gamma

KW - Middle Aged

KW - RNA, Messenger

KW - Thyroid Gland

M3 - SCORING: Journal article

C2 - 9218831

VL - 109

SP - 98

EP - 106

JO - CLIN EXP IMMUNOL

JF - CLIN EXP IMMUNOL

SN - 0009-9104

IS - 1

ER -