
마우스 면역 체계를 가진 사람 면역 시스템 마우스에서 PD-1+CD4+ 말초 도움 T 세포 유사 세포와 여포 도움 T 세포 유사 세포가 자가면역 질환을 유발한다.


coremsg

Human immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants and immunotherapies. In HIS mice that generate T cells de novo from hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg- Prkdc scid Il2rg tm1Wjl (NSG) mouse thymus, where negative selection is abnormal. Disease develops very late when human T cells develop in human fetal thymus grafts, where robust negative selection is observed. We demonstrate here that PD-1+CD4+ peripheral (Tph) helper-like and follicular (Tfh) helper-like T cells developing in HIS mice can induce autoimmune disease. Tfh-like cells were more prominent in HIS mice with a mouse thymus, in which the highest levels of IgG were detected in plasma, compared to those with a human thymus. While circulating IgG and IgM antibodies were autoreactive to multiple mouse antigens, in vivo depletion of B cells and antibodies did not delay the development of autoimmune disease. Conversely, adoptive transfer of enriched Tfh- or Tph-like cells induced disease and autoimmunity-associated B cell phenotypes in recipient mice containing autologous human APCs without T cells. T cells from mice with a human thymus expanded and induced disease more rapidly than those originating in a murine thymus, implicating HLA-restricted T cell-APC interactions in this process. Since Tfh, Tph, autoantibodies and LIP have all been implicated in various forms of human autoimmune disease, the observations here provide a platform for the further dissection of human autoimmune disease mechanisms and therapies.

### Competing Interest Statement

The authors have declared no competing interest.

Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice

마우스-면역-체계를-가진-사람-면역-시스템-마우스에서-여포-도움-t-세포와-말초-도움-t-세포-유사-세포가-자가면역-질환을-유발한다


마우스 면역 체계를 가진 사람 면역 시스템 마우스에서 여포 도움 T 세포와 말초 도움 T 세포 유사 세포가 자가면역 질환을 유발한다
