Role of the thymus in spontaneous development of a multi-organ autoimmune disease in human immune system mice.
Role of the thymus in spontaneous development of a multi-organ autoimmune disease in human immune system mice.
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DOI：
10.1016/j.jaut.2021.102612
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发表时间：
2021-05
影响因子：
12.8
通讯作者：
Sykes M
中科院分区：
文献类型：
--
作者：
Khosravi-Maharlooei M;Li H;Hoelzl M;Zhao G;Ruiz A;Misra A;Li Y;Teteloshvili N;Nauman G;Danzl N;Ding X;Pinker EY;Obradovic A;Yang YG;Iuga A;Creusot RJ;Winchester R;Sykes M
We evaluated the role of the thymus in development of multi-organ autoimmunity in human immune system (HIS) mice. T cells were essential for disease development and the same T cell clones with varying phenotypes infiltrated multiple tissues. De novo-generated hematopoietic stem cell (HSC)-derived T cells were the major disease drivers, though thymocytes pre-existing in grafted human thymi contributed if not first depleted. HIS mice with a native mouse thymus developed disease earlier than thymectomized mice with a thymocyte-depleted human thymus graft. Defective structure in the native mouse thymus was associated with impaired negative selection of thymocytes expressing a transgenic TCR recognizing a self-antigen. Disease developed without direct recognition of antigens on recipient mouse MHC. While human thymus grafts had normal structure and negative selection, failure to tolerize human T cells recognizing mouse antigens presented on HLA molecules may explain eventual disease development. These new insights have implications for human autoimmunity and suggest methods of avoiding autoimmunity in next-generation HIS mice.
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影响因子：
46.9
作者：
Han, Arnold;Glanville, Jacob;Hansmann, Leo;Davis, Mark M.
通讯作者：
Davis, Mark M.
影响因子：
4.6
作者：
Covassin, L.;Jangalwe, S.;Brehm, M. A.
通讯作者：
Brehm, M. A.
影响因子：
30.5
作者：
Aschenbrenner, Katharina;D'Cruz, Louise M.;Klein, Ludger
通讯作者：
Klein, Ludger
影响因子：
4.8
作者：
Brehm, Michael A.;Kenney, Laurie L.;Shultz, Leonard D.
通讯作者：
Shultz, Leonard D.
影响因子：
17.1
作者：
Kalscheuer H;Danzl N;Onoe T;Faust T;Winchester R;Goland R;Greenberg E;Spitzer TR;Savage DG;Tahara H;Choi G;Yang YG;Sykes M
通讯作者：
Sykes M