Single blood transfusion induces the production of donor-specific alloantibodies and regulatory T cells mainly in the spleen.

Single blood transfusion induces the production of donor-specific alloantibodies and regulatory T cells mainly in the spleen.
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DOI:
10.1093/intimm/dxx078
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发表时间:
2018-03-08
影响因子:
4.4
通讯作者:
Matsuno K
Matsuno K
中科院分区:
医学3区
文献类型:
--
作者:
Ueta H;Kitazawa Y;Sawanobori Y;Ueno T;Ueha S;Matsushima K;Matsuno K

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单次供体特异性输血诱导同种抗体和Treg细胞已知供体特异性输血诱导同种反应并导致免疫抑制。我们研究了其潜在的机制,采用完全同种异体大鼠组合。输血受体有效地产生针对供体I类MHC的IgM和IgG亚类的同种抗体。受者脾脏中CD 4 + T细胞和CD 4 + FOXP 3+调节性T细胞(Treg细胞)活跃扩增,其次是CD 45 R + B细胞和IgM+或IgG亚类+抗体形成细胞。从1.5d开始,脾T细胞区(动脉周围淋巴细胞鞘)的MHCII+ CD 103+树突状细胞(DC)与受体BrdU+或5-乙炔基-2 ′-脱氧尿苷+细胞形成簇,CD 4 + T细胞的增殖反应在3- 4d达到高峰。输血诱导的抗体在体外和体内具有供体乘客细胞消耗活性,并且可以抑制由供体T细胞引起的急性GvH疾病。此外,Treg细胞以供体特异性方式显著抑制混合白细胞反应。总之,单次输血有效地诱导辅助T细胞依赖性抗供体I类MHC抗体形成细胞反应,免疫球蛋白类别转换,和供体特异性Treg细胞反应,主要在脾脏中,可能通过间接同种异体识别通过居民DC。这些抗体和Treg细胞可能至少部分参与供体特异性输血诱导的同种异体移植排斥反应抑制。
A single donor-specific transfusion induces alloantibodies and Treg cells Donor-specific blood transfusion is known to induce alloresponses and lead to immunosuppression. We examined their underlying mechanisms by employing fully allogeneic rat combinations. Transfused recipients efficiently produced alloantibodies of the IgM and IgG subclasses directed against donor class I MHC. The recipients exhibited active expansion of CD4+ T cells and CD4+FOXP3+ regulatory T cells (Treg cells), followed by CD45R+ B cells and IgM+ or IgG subclass+ antibody-forming cells mainly in the spleen. From 1.5 days, the resident MHCII+CD103+ dendritic cells (DCs) in the splenic T-cell area, periarterial lymphocyte sheath, formed clusters with recipient BrdU+ or 5-ethynyl-2′-deoxyuridine+ cells, from which the proliferative response of CD4+ T cells originated peaking at 3–4 days. Transfusion-induced antibodies had donor passenger cell-depleting activity in vitro and in vivo and could suppress acute GvH disease caused by donor T cells. Furthermore, Treg cells significantly suppressed mixed leukocyte reactions in a donor-specific manner. In conclusion, single blood transfusion efficiently induced a helper T-cell-dependent anti-donor class I MHC antibody-forming cell response with immunoglobulin class switching, and a donor-specific Treg cell response mainly in the spleen, probably by way of the indirect allorecognition via resident DCs. These antibodies and Treg cells may be involved, at least partly, in the donor-specific transfusion-induced suppression of allograft rejection.
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