CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis.
CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis.
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DOI：
10.1084/jem.20011565
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发表时间：
2002-05-20
期刊：
影响因子：
--
通讯作者：
Weyand CM
中科院分区：
文献类型：
--
作者：
Kang YM;Zhang X;Wagner UG;Yang H;Beckenbaugh RD;Kurtin PJ;Goronzy JJ;Weyand CM
类风湿性关节炎中炎性病变的组装受到高度调节，通常导致具有生发中心（GC）反应的淋巴滤泡的形成。我们使用显微解剖这种结节性卵泡来分析定居的T细胞。虽然滤泡T细胞的库是多样的，T细胞受体（TCR）序列的一个子集中检测到多个独立的卵泡，而不是在滤泡间区，这表明识别一个共同的抗原。出乎意料的是，大多数共享TCR序列来自高度富集在滑膜中并且以低数量存在于外周中的CD 8 T细胞。为了检查它们在结节GC反应中的作用，在人滑膜-SCID小鼠嵌合体中耗尽CD 8 T细胞。滑膜CD 8 T细胞的耗竭导致含GC的卵泡解体。在缺乏CD 8 T细胞的情况下，滤泡树突状细胞消失，光敏素-α1β2的产生显著减少，免疫球蛋白（IG）分泌停止。免疫组织化学研究表明，这些CD 8 T细胞聚集在外套带的边缘。除了它们独特的定位之外，它们的特征在于产生干扰素（IFN）-γ、缺乏孔形成酶穿孔素和表达CD 40配体。滤泡周围IFN-γ+ CD 8 T细胞在次级淋巴组织中很少，但在滑膜浸润中占IFN-γ+细胞的大多数。我们建议，CD 8 + T细胞调节异位淋巴滤泡中GC的结构完整性和功能活性。
The assembly of inflammatory lesions in rheumatoid arthritis is highly regulated and typically leads to the formation of lymphoid follicles with germinal center (GC) reactions. We used microdissection of such extranodal follicles to analyze the colonizing T cells. Although the repertoire of follicular T cells was diverse, a subset of T cell receptor (TCR) sequences was detected in multiple independent follicles and not in interfollicular zones, suggesting recognition of a common antigen. Unexpectedly, the majority of shared TCR sequences were from CD8 T cells that were highly enriched in the synovium and present in low numbers in the periphery. To examine their role in extranodal GC reactions, CD8 T cells were depleted in human synovium-SCID mouse chimeras. Depletion of synovial CD8 T cells caused disintegration of the GC-containing follicles. In the absence of CD8 T cells, follicular dendritic cells disappeared, production of lymphotoxin-α1β2 markedly decreased, and immunoglobulin (Ig) secretion ceased. Immunohistochemical studies demonstrated that these CD8 T cells accumulated at the edge of the mantle zone. Besides their unique localization, they were characterized by the production of interferon (IFN)-γ, lack of the pore-forming enzyme perforin, and expression of CD40 ligand. Perifollicular IFN-γ+ CD8 T cells were rare in secondary lymphoid tissues but accounted for the majority of IFN-γ+ cells in synovial infiltrates. We propose that CD8+ T cells regulate the structural integrity and functional activity of GCs in ectopic lymphoid follicles.
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DOI：
10.1186/ar80
发表时间：
2000
期刊：
Arthritis research
影响因子：
--
作者：
Tan LC;Mowat AG;Fazou C;Rostron T;Roskell H;Dunbar PR;Tournay C;Romagné F;Peyrat MA;Houssaint E;Bonneville M;Rickinson AB;McMichael AJ;Callan MF
通讯作者：
Callan MF
影响因子：
15.3
作者：
Itoh, K;Meffre, E;Chiorazzi, N
通讯作者：
Chiorazzi, N
影响因子：
7.8
作者：
Kelsoe, G
通讯作者：
Kelsoe, G
T细胞对慢性类风湿关节炎中爱泼斯坦 - 巴尔病毒反式激活剂的反应。
DOI：
10.1084/jem.184.5.1791
发表时间：
1996-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Ruddle, NH
通讯作者：
Ruddle, NH