The influence of triiodothyronine, thyroxine, thyrotropin, and methimazole on thyroid cell MHC class II antigen expression.
We have studied the influence of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and methimazole (MMI) on the expression of major histocompatibility (MHC) Class II antigen expression in human thyroid cells. T3, T4, TSH, and MMI in various combinations were added together with interferon-gamma (IFN-gamma) to human thyrocytes or to cultured FRTL-5 cells. Neither T3 nor T4, alone, caused inhibition of the IFN-gamma stimulation of thyrocyte HLA-DR expression. Moreover, the combination of both drugs at various concentrations did not inhibit this expression except only in low ranges (T3 at 0.3 nmol/liter and T4 at 12.9 nmol/liter). MMI only at a concentration of 3.0 mmol/liter caused significant inhibition of IFN-gamma-induced HLA-DR expression. However, the addition of T3 (range, 0.3-9.2 nmol/liter) or T4 (12.9-129.0 nmol/liter) prevented the MMI-induced inhibition. This phenomenon may be explained by the action of MMI on inhibiting the synthesis of T3 and T4. At a concentration of 100 microU/ml, TSH enhanced IFN-gamma-induced HLA-DR expression. It is possible that TSH induced the expression of large numbers of IFN-gamma receptors, thereby enhancing the production of HLA-DR in response to IFN-gamma. Our studies suggest that MMI does not alter thyrocyte HLA-DR expression in vitro, especially when combined with T3 or T4; however, MMI may still induce or perpetuate immune effects in vivo secondary to its influence on thyroid hormone production or thyroid antigen presentation.
Atwa
M A
MA
Department of Medicine, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
Lukes
Y D
YD
Salata
K
K
Abo-Hashem
E M
EM
el-Kannishy
M H
MH
Burman
K D
KD
D000818:Animals; D002460:Cell Line; D006684:HLA-DR Antigens / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D008713:Methimazole / Q000494:pharmacology*; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism*; D013963:Thyroid Hormones / Q000502:physiology*; D013972:Thyrotropin / Q000502:physiology; D013974:Thyroxine / Q000502:physiology; D014284:Triiodothyronine / Q000502:physiology
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D013963:Thyroid Hormones; D014284:Triiodothyronine; D008713:Methimazole; D007371:Interferon-gamma; D013972:Thyrotropin; D013974:Thyroxine