CD154 blockade abrogates allospecific responses and enhances CD4(+) regulatory T-cells in mouse orthotopic lung transplant.
CD154 blockade abrogates allospecific responses and enhances CD4(+) regulatory T-cells in mouse orthotopic lung transplant.
复制标题
DOI：
10.1111/j.1600-6143.2011.03623.x
复制
发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
McDyer JF
中科院分区：
文献类型：
--
作者：
Dodd-o JM;Lendermon EA;Miller HL;Zhong Q;John ER;Jungraithmayr WM;D'Alessio FR;McDyer JF
急性细胞排斥反应（acute cellular rejection，ACR）是肺移植术后常见而重要的临床并发症.虽然临床上需要开发新的疗法来预防ACR，但对该过程中同种特异性效应T细胞的调节仍不完全清楚。使用MHC不匹配的小鼠原位肺移植模型，我们研究了抗CD 154单克隆抗体单独治疗对同种异体移植病理学和同种免疫T细胞效应反应的短期作用。与同系移植物对照组相比，未治疗的BALB/c左肺同种异体移植物的C57 BL/6受体具有高度排斥和降低的CD 4+：CD 8+移植物比率，其特征在于在第10天主要是CD 8 +> CD 4 + IFN-γ+同种异体特异性效应物应答。抗CD 154单克隆抗体治疗显著消除了CD 8+和CD 4+同种异体效应反应，并显著增加了肺同种异体移植物CD 4+：CD 8+比值。移植物CD 4 + T细胞的检查显示，抗CD 154处理的小鼠的肺同种异体移植物中CD 4 + CD 25 + Foxp 3+调节性T细胞的频率显著增加，并且与未处理的对照相比，与ACR的显著减弱相关。总之，这些数据表明，单独的CD 154/CD 40共刺激阻断足以消除同种异体特异性效应T细胞应答，并使肺同种异体移植物向与ACR衰减相关的CD 4 + T调节细胞占主导地位的环境显著转移。
Acute cellular rejection (ACR) is a common and important clinical complication following lung transplantation. While there is a clinical need for the development of novel therapies to prevent ACR, the regulation of allospecific effector T cells in this process remains incompletely understood. Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated the short-term role of anti-CD154 mAb therapy alone on allograft pathology and alloimmune T cell effector responses. Untreated C57BL/6 recipients of BALB/c left lung allografts had high-grade rejection and diminished CD4+:CD8+ graft ratios, marked by predominantly CD8+>CD4+ IFN-γ+ allospecific effector responses at day 10, compared to isograft controls. Anti-CD154 mAb therapy strikingly abrogated both CD8+ and CD4+ alloeffector responses and significantly increased lung allograft CD4+:CD8+ ratios. Examination of graft CD4+ T cells revealed significantly increased frequencies of CD4+CD25+Foxp3+ regulatory T cells in the lung allografts of anti-CD154-treated mice and was associated with significant attenuation of ACR compared to untreated controls. Together, these data show that CD154/CD40 costimulation blockade alone is sufficient to abrogate allospecific effector T cell responses and significantly shifts the lung allograft toward an environment predominated by CD4+ T regulatory cells in association with an attenuation of ACR.
登录
查看更多内容
树突状细胞对于维持流感病毒感染小鼠肺部的三级淋巴结构至关重要。
DOI：
10.1084/jem.20090410
发表时间：
2009-10-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
GeurtsvanKessel CH;Willart MA;Bergen IM;van Rijt LS;Muskens F;Elewaut D;Osterhaus AD;Hendriks R;Rimmelzwaan GF;Lambrecht BN
通讯作者：
Lambrecht BN
介导同种异体移植耐受性的FOXP3+ T调节细胞的募集取决于CCR4趋化因子受体。
影响因子：
15.3
作者：
Lee, I;Wang, LQ;Wells, AD;Dorf, ME;Ozkaynak, E;Hancock, WW
通讯作者：
Hancock, WW
影响因子：
6.2
作者：
Markees, TG;Phillips, NE;Rossini, AA
通讯作者：
Rossini, AA
影响因子：
6.2
作者：
Ensminger, SM;Witzke, O;Wood, KJ
通讯作者：
Wood, KJ
影响因子：
4.4
作者：
Gelman, Andrew E.;Okazaki, Mikio;Kreisel, Daniel
通讯作者：
Kreisel, Daniel