
ヒト免疫システムマウスにおいて、濾胞性ヘルパーT細胞様細胞とペリフェラルヘルパーT細胞様細胞が自己抗体産生を誘導し、自己免疫疾患の発症に重要な役割を果たす。


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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

マウス免疫システムを持つヒト免疫システムマウスにおける濾胞性ヘルパーt細胞様細胞とペリフェラルヘルパーt細胞様細胞が自己免疫疾患を引き起こす


マウス免疫システムを持つヒト免疫システムマウスにおける濾胞性ヘルパーT細胞様細胞とペリフェラルヘルパーT細胞様細胞が自己免疫疾患を引き起こす


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CD8+T細胞の自己認識能力を示すCD5の発現レベルは、これらT細胞の活性化、増殖、および自己免疫疾患への寄与を決定する。


Our understanding of autoimmune diabetes underscores the critical involvement of CD8+ T cells recognizing islet-specific antigens. However, the influence of thymic positive selection on diabetogenic CD8+ T cell development remains unclear. Using CD5 marker representing T-cell receptor (TCR) signal strength, we illustrated that naïve CD5hiCD8+ T cells of non-obese diabetic (NOD) mice with enhanced TCR signals displayed predisposed differentiated/memory T cell traits with increased activation and proliferation upon TCR stimulation, compared to CD5lo counterparts. Additionally, CD5hiCD8+ T cells exhibited gene expression landscape similar to effector T cells and exacerbated disease in transfer model. Interestingly, the protective effects of transgenic phosphatase Pep expression, which lowers TCR signaling and diabetes incidence, were abolished in NOD strain 8.3 with high CD5 expression linked to increased thymic positive selection. Strikingly, TCR repertoire analysis identified higher frequencies of autoimmune disease-related clonotypes in naïve CD5hiCD8+ cells, supporting that distinct effector functions arise from intrinsic TCR repertoire differences. Overall, CD5hiCD8+ clones may be potential targets for autoimmune diabetes treatment.

### Competing Interest Statement

The authors have declared no competing interest.

*   dLPC/NOD
    :   Lck distal promoter– Ptpn22 C line in NOD background
    dLPE/NOD
    :   Lck distal promoter– Ptpn22 E line in NOD background
    NOD
    :   non-obese diabetic

Thymic self-recognition-mediated TCR signal strength modulates antigen-specific CD8+ T cell pathogenicity in non-obese diabetic mice

自己認識によって調節されるt細胞受容体シグナル強度が-非肥満性糖尿病マウスにおける抗原特異的cd8-t細胞の病原性を調節する


自己認識によって調節されるT細胞受容体シグナル強度が、非肥満性糖尿病マウスにおける抗原特異的CD8+T細胞の病原性を調節する



SSc患者における抗Ro/SSA抗体の存在は、ILDのリスク因子であり、ILD発症のスクリーニングに役立つ可能性がある。


Anti-Ro/SSA antibodies predicted which patients were at most risk for ILD but not ILD progression or overall disease progression and death.

Anti-Ro/SSA Antibodies Have Potential to Predict ILD in SSc

ssc患者におけるild予測のための抗ro-ssa抗体の有用性


SSc患者におけるILD予測のための抗Ro/SSA抗体の有用性
