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Minor contribution of cytotoxic T lymphocyte antigen 4 and programmed cell death 1 ligand 1 in immune tolerance against mouse thyrotropin receptor in mice


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タイトル: Minor contribution of cytotoxic T lymphocyte antigen 4 and programmed cell death 1 ligand 1 in immune tolerance against mouse thyrotropin receptor in mice
著者: Yasui, Junichi / Nakahara, Mami / Shimamura, Mika / Kurashige, Tomomi / Yasui, Kazuaki / Abiru, Norio / Kawakami, Atsushi / Nagayama, Yuji
発行日: 2014年 7月
出版者: Nagasaki University School of Medicine / 長崎大学医学部
引用: Acta medica Nagasakiensia, 59(1), pp.13-17; 2014
抄録: We have previously shown that wild type (wt) mice exhibit susceptibility to immunization with human (h) thyrotropin receptor (TSHR), but resistance to mouse (m) TSHR, while TSHR knockout (KO) mice are susceptible to mTSHR, indicating the existence of robust immune tolerance against the mTSHR in wt mice. This tolerance may be mediated by either centrally or peripherally. We here explored the contribution of a peripheral arm of immune tolerance against the mTSHR by using antibodies to deplete regulatory T cells (Tregs), to antagonize co-inhibitory molecules and/or to stimulate co-stimulatory molecules. Antagonistic anti-co-inhibitory molecules, cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 ligand 1 (PDL1), induced only low levels of anti-TSHR antibodies without induction of hyperthyroidism in a mouse Graves'model. In this experimental setting, antibody levels were significantly higher in THSR+/- mice than wt mice. However, agonistic anti-co-stimulatory molecules, CD40 and CD137, and Treg-depleting anti-CD25 antibodies showed no effect. All these data suggest that peripheral immune tolerance against the mTSHR may play a minor role, and imply the importance of central tolerance, in immune tolerance against mTSHR in mice. Additional studies on central tolerance to the mTSHR will be necessary for completely delineating the mechanisms for immune tolerance against mTSHR in mice.
キーワード: thyrotropin receptor / CTLA-4 / PD-L 1 / Grave's disease
URI: http://hdl.handle.net/10069/34696
ISSN: 00016055
資料タイプ: Departmental Bulletin Paper
原稿種類: publisher
出現コレクション:Volume 59, No. 1

引用URI : http://hdl.handle.net/10069/34696

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