Donor CD8 T cell activation is critical for greater renal disease severity in female chronic graft-vs.-host mice and is associated with increased splenic ICOS(hi) host CD4 T cells and IL-21 expression.
Donor CD8 T cell activation is critical for greater renal disease severity in female chronic graft-vs.-host mice and is associated with increased splenic ICOS(hi) host CD4 T cells and IL-21 expression.
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DOI：
10.1016/j.clim.2010.01.005
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发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Via CS
中科院分区：
文献类型：
--
作者：
Foster AD;Haas M;Puliaeva I;Soloviova K;Puliaev R;Via CS
DBA/2-into-F1（DBA→F1）小鼠中的狼疮样肾病由供体CD 4 T细胞驱动，并且在雌性中更严重。供体CD 8 T细胞没有已知的作用。正如预期的那样，我们观察到，与雄性相比，接受未分级DBA脾细胞（CD 8完整→F1）的雌性在13周时表现出更大的肾脏疾病临床和组织学严重程度。令人惊讶的是，由于雌性改善和雄性恶化，CD 8耗竭→F1小鼠中肾脏疾病严重程度的性别差异消失。CD 8完整→F1雌性小鼠的供体和宿主效应（CD 44 hi、CD 62 Llo）CD 4 T细胞和ICOShi CD 4滤泡辅助T细胞显著高于雄性小鼠。与雄性小鼠相比，CD 8耗竭→F1雌性小鼠的宿主（但非供体）CD 4 Tfh细胞绝对数量减少，并且宿主CD 4效应细胞的显著增加消失。在CD 8完整→F1小鼠中观察到更高的雌性IL-21表达（Tfh细胞的产物），尽管降低，但仍高于雄性CD 8缺失→F1小鼠。因此，供体CD 8 T细胞在介导基于性别的狼疮肾病严重程度差异中具有关键作用，这可能是通过更大的宿主ICOShi CD 4 T细胞参与。
Lupus-like renal disease in DBA/2-into-F1 (DBA→F1) mice is driven by donor CD4 T cells and is more severe in females. Donor CD8 T cells have no known role. As expected, we observed that females receiving unfractionated DBA splenocytes (CD8 intact→F1) exhibited greater clinical and histological severity of renal disease at 13 weeks compared to males. Surprisingly, sex based differences in renal disease severity were lost in CD8 depleted→F1 mice due to an improvement in females and a worsening in males. CD8 intact →F1 female mice exhibited significantly greater donor and host effector (CD44hi, CD62Llo) CD4 T cells and ICOShi CD4 T follicular helper cells than males. CD8 depleted→F1 female mice exhibited a reduction in the absolute numbers of host, but not donor CD4 Tfh cells and lost the significant increase in host CD4 effector cells vs. males. Greater female IL-21 expression, a product of Tfh cells, was seen in CD8 intact→F1 and although reduced was still greater than male CD8 depleted →F1 mice. Thus, donor CD8 T cells have a critical role in mediating sex based differences in lupus renal disease severity possibly through greater host ICOShi CD4T cell involvement.
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影响因子：
15.9
作者：
PASSWELL, J;SCHREINER, GF;COLTEN, HR
通讯作者：
COLTEN, HR
影响因子：
4.4
作者：
Puliaev, Roman;Puliaeva, Irina;Welniak, Lisbeth A.;Ryan, Abigail E.;Haas, Mark;Murphy, William J.;Via, Charles S.
通讯作者：
Via, Charles S.
影响因子：
32.4
作者：
Nurieva, Roza I.;Chung, Yeonseok;Hwang, Daehee;Yang, Xuexian O.;Kang, Hong Soon;Ma, Li;Wang, Yi-Hong;Watowich, Stephanie S.;Jetten, Anton M.;Tian, Qiang;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
6.5
作者：
GLEICHMANN, E;GLEICHMANN, H
通讯作者：
GLEICHMANN, H
影响因子：
3.6
作者：
Niculescu, F;Niculescu, T;Via, CS
通讯作者：
Via, CS