T cell depletion increases humoral response by favoring T follicular helper cells expansion.
T cell depletion increases humoral response by favoring T follicular helper cells expansion.
复制标题
T细胞耗竭通过有利于T滤泡辅助细胞扩增而增加体液应答。
DOI：
10.1111/ajt.17038
复制
发表时间：
2022-07
影响因子：
8.8
通讯作者：
Riella, Leonardo V.
中科院分区：
文献类型：
--
作者：
Gassen, Rodrigo Benedetti;Borges, Thiago J.;Perez-Saez, Maria Jose;Zhang, Hengcheng;Al Jurdi, Ayman;Llinas-Mallol, Laura;Aoyama, Bruno;Lima, Mauricio;Pascual, Julio;Sage, Peter T.;Murakami, Naoka;Riella, Leonardo V.
关键词：
抗体介导的排斥反应是肾移植患者长期移植物丢失的主要原因。滤泡辅助性T细胞（Tfh）对于辅助B细胞分化是至关重要的，并且是有效的抗体应答所需的。抗胸腺细胞球蛋白（ATG）是一种广泛使用的淋巴细胞耗竭诱导治疗。然而，关于ATG如何影响Tfh细胞发育和供体特异性抗体（DSA）形成的研究知之甚少。我们观察到接受ATG的患者在肾移植后6个月循环Tfh细胞增加。使用NP-OVA免疫模型，我们发现与对照组相比，ATG处理的小鼠具有更高百分比的Tfh细胞、生发中心B细胞和更高滴度的抗原特异性抗体。ATG处理的动物具有较低水平的IL-2（一种已知的Bcl-6阻遏物），但具有较高水平的IL-21、pSTAT 3和Bcl-6，有利于Tfh分化。在小鼠肾移植模型中，ATG处理的受体显示出同种异体移植物中Tfh细胞、DSA和C4d染色的增加。尽管ATG在耗尽T细胞方面是有效的，但其有利于耗尽后Tfh细胞的扩增。同时使用IL-2，他克莫司，雷帕霉素与ATG是必不可少的控制Tfh细胞扩增。总之，ATG耗竭有利于Tfh扩增，增强抗体介导的应答。
Antibody-mediated rejection is a major cause of long-term graft loss in kidney transplant patients. T follicular helper (Tfh) cells are crucial for assisting B cell differentiation and are required for an efficient antibody response. Anti-thymocyte globulin (ATG) is a widely used lymphocyte-depleting induction therapy. However, little is known about how ATG affects Tfh cell development and donor-specific antibody (DSA) formation. We observed an increase in circulating Tfh cells at 6 months after kidney transplant in patients who received ATG. Using an NP-OVA immunization model, we found that ATG-treated mice had a higher percentage of Tfh cells, germinal center B cells, and higher titers of antigen-specific antibodies compared to controls. ATG-treated animals had lower levels of IL-2, a known Bcl-6 repressor, but higher levels of IL-21, pSTAT3 and Bcl-6, favoring Tfh differentiation. In a mouse kidney transplant model, ATG-treated recipients showed an increase in Tfh cells, DSA and C4d staining in the allograft. Although ATG was effective in depleting T cells, it favored the expansion of Tfh cells following depletion. Concomitant use of IL-2, tacrolimus, or rapamycin with ATG was essential to control Tfh cell expansion. In summary, ATG depletion favors Tfh expansion, enhancing antibody-mediated response.
登录
查看更多内容
影响因子：
30.5
作者：
Clement, Rachel L.;Daccache, Joe;Sage, Peter T.
通讯作者：
Sage, Peter T.
DOI：
10.1084/jem.20141380
发表时间：
2015-04-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hatzi K;Nance JP;Kroenke MA;Bothwell M;Haddad EK;Melnick A;Crotty S
通讯作者：
Crotty S
影响因子：
8.8
作者：
Hart, A.;Lentine, K. L.;Snyder, J. J.
通讯作者：
Snyder, J. J.
影响因子：
3.7
作者：
Grafals, Monica;Smith, Brian;Riella, Leonardo V.
通讯作者：
Riella, Leonardo V.
影响因子：
8.8
作者：
Luis Cano-Romero, Francisco;Laguna Goya, Rocio;Paz-Artal, Estela
通讯作者：
Paz-Artal, Estela