Abstract： Objective To study the effects of prolactin(PRL) on HLA-DR and CD40 expressions by human thyrocytes,and to investigate the possible mechanisms for PRL to affect the development of Graves'disease(GD).Methods Thyrocytes in secondary culture,which were from GD thyroid glands the tissues adjacent to the lwesions of multinodular goiter and andenoma(control group),were treated respectively with ovine PRL (oPRL),interferon-γ(IFN-γ),interlukin-4(IL-4)and oPRL plus IFN-γ(10U/ml)or IL-4(5ng/ml)for 7days.HLA-DR and CD40 expressions on the thyrocytes were determined by immunofluorescent staining and flow cytometry. Results oPRL(12.5ng/ml-1000ng/ml)had no significant direct effect on HLA-DR or CD40 expression.It did not significantly affect the stimulation of HLA-DR expressions on the rwo groups of thyrocyte treated with IFN-γ or on GD thyrocytes treated with IL-4.oPRL could antagonize the stimulation of CD40 expressions by IFN-γ and the inhibition by IL-4 on both groups of thyrocytes.The antagonizing effects were related to the concentration of PRL.IFN-γ-stimulated percentages of CD40+ thyrocytes and delta mean fluorescence intensity(dMF)in both thyrocyte sources were significantly reduced in the presence of 200ng/ml oPRL(both GD and Control:P<0.01and P<0.05,respectively;Control:P<0.05)and 1000ng/ml oPRL(GD:P<0.01;Control:P<0.05).oPRL caused significant increasing in IL-4-inhibited percentages of CD40+ cells from the two groups of thyrocytes at 12.5ng/ml and 1000ng/ml and dMF from GD thyrocytes at 1000ng/ml(P<0.05).Conclusions PRL can exert indirect effects on CD40 expressions on thyrocytes by antagonizing the modulatory actions of IFN-γand IL-4 with dose-related effects.This may be one important mechanism for PRL to affect the development of GD.