Estimation of Sensitization Status in Renal Transplant Recipients by Assessing Indirect Pathway CD4+ T Cell Response to Donor Cell-pulsed Dendritic Cell
Estimation of Sensitization Status in Renal Transplant Recipients by Assessing Indirect Pathway CD4+ T Cell Response to Donor Cell-pulsed Dendritic Cell
复制标题
通过评估间接途径 CD4 T 细胞对供体细胞脉冲树突状细胞的反应来估计肾移植受者的致敏状态
DOI：
10.1097/tp.0000000000004491
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发表时间：
2023
期刊：
影响因子：
6.2
通讯作者：
Takaaki Kobayashi
中科院分区：
文献类型：
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作者：
Kenta Iwasaki;Toshihide Tomosugi;Takashi Sekiya;Shintaro Sakamoto;Yuko Miwa;Manabu Okada;Takahisa Hiramitsu;Norihiko Goto;Shunji Narumi;Yoshihiko Watarai;Mai Okumura;Satoshi Ashimine;Kohei Ishiyama;Ezzelarab Mohamed B.;Takaaki Kobayashi
背景：通过间接同种异体识别产生供者特异性人类白细胞抗原抗体（DSA）对移植器官的长期存活是有害的。检测到这种免疫反应将有可能确定具有高致敏风险的患者。在这项研究中，我们建立了一种新的方法来评估间接同种异体识别评估致敏在肾移植recipient.Methods. CD 14+单核细胞与供体外周血单核细胞混合，在IL-4，GM-CSF，IL-1β和TNFα的存在下培养，并用作脉冲树突状细胞（DC）。结果：同种抗原致敏的DC与CD 4 + T细胞共培养后，细胞增殖明显增强，产生IFN-γ和IL-21。约1%的CD 4 + T细胞表现出Tfh样表型（PD-1高CXCR 5 + ICOS+ CD 40 L+）。用供体外周血单核细胞脉冲的CD 45 RA + CD 4+和CD 45 RA-CD 4+（通常分别定义为人类的幼稚和记忆）T细胞共培养。无论预先形成或从头DSA状态，CD 45 RA + CD 4 + T细胞持续产生IL-21。相比之下，预先DSA阳性患者中IL-21产生的CD 45 RA − CD 4 + T细胞显著高于阴性患者（80.8±51.2 vs 14.8±20.4，P< 0.001）。在新生DSA阳性患者中，与移植前相比，移植后IL-21产生的CD 45 RA − CD 4 + T细胞显著增加（9.23± 9.08vs43.9 ±29.1，P< 0.001）。结论：间接途径的CD 4 + T细胞反应的评估可以为新生DSA产生的潜在机制提供新的见解，从而导致对抗抗体介导的排斥反应的有效策略的发展。
Background.Generation of donor-specific human leukocyte antigen antibody (DSA) via indirect allorecognition is detrimental to long-term survival of transplant organs. The detection of such immune responses would make it possible to define patients with high risk of sensitization. In this study, we established a novel method for evaluating indirect allorecognition to assess sensitization in kidney transplant recipients.Methods.Recipient CD14+ monocytes were mixed with donor peripheral blood mononuclear cells; cultured in the presence of IL-4, GM-CSF, IL-1β, and TNFα; and used as pulsed dendritic cells (DCs). Cell proliferation and cytokine production were evaluated by carboxyfluorescein diacetate succinimidyl ester–based T cell proliferation assay and Enzyme-Linked ImmunoSpot assay, respectively.Results.CD4+ T cell proliferation was strongly observed in following coculture with allogeneic antigen-pulsed DC leading to interferon-γ and IL-21 production. About 1% of CD4+ T cells exhibited Tfh-like phenotype (PD-1 high CXCR5+ ICOS+ CD40L+). Recipient DC pulsed with donor peripheral blood mononuclear cells was cocultured with recipient CD45RA+ CD4+ and CD45RA-CD4+(generally defined as naive and memory in humans, respectively) T cells. Irrespective of preformed or de novo DSA status, CD45RA+ CD4+ T cells constantly produced IL-21. In contrast, IL-21–produced CD45RA− CD4+ T cells were significantly higher in preformed DSA-positive patients than those in negative patients (80.8±51.2 versus 14.8±20.4, P< 0.001). In de novo DSA-positive patients, IL-21–produced CD45RA− CD4+ T cells were significantly increased after transplantation compared with before transplantation (9.23±9.08 versus 43.9±29.1, P< 0.001).Conclusions.Assessment of indirect pathway CD4+ T cell response could provide new insights into the underlying mechanism of de novo DSA production, leading to the development of effective strategies against antibody-mediated rejection.
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影响因子：
15.9
作者：
Liu, Quan;Rojas-Canales, Darling M.;Morelli, Adrian E.
通讯作者：
Morelli, Adrian E.
影响因子：
6.2
作者：
Breman E;van Miert PP;van der Steen DM;Heemskerk MH;Doxiadis II;Roelen D;Claas FH;van Kooten C
通讯作者：
van Kooten C
影响因子：
4.4
作者：
Markey, Kate A.;Koyama, Motoko;Hill, Geoffrey R.
通讯作者：
Hill, Geoffrey R.
影响因子：
4.6
作者：
Yazdani M;Gholizadeh Z;Nikpoor AR;Mohamadian Roshan N;Jaafari MR;Badiee A
通讯作者：
Badiee A
使用 PIRCHE-II 算法评估预制供体 HLA 反应性 T 细胞
DOI：
--
发表时间：
2020
期刊：
影响因子：
--
作者：
T. Tomosugi;K. Iwasaki;S. Sakamoto;A. Kanda;K. Futamura;M. Okada;T. Hiramitsu;N. Goto;S. Narumi;Y. Watarai;T. Kobayashi;M. Niemann;E. Spierings
通讯作者：
E. Spierings