Role of gamma delta T cells in murine collagen-induced arthritis.
Role of gamma delta T cells in murine collagen-induced arthritis.
复制标题
DOI：
10.4049/jimmunol.151.11.6546
复制
发表时间：
1993-12
影响因子：
4.4
通讯作者：
G. Peterman;C. Spencer;Anne I. Sperling;J. A. Bluestone
中科院分区：
文献类型：
--
作者：
G. Peterman;C. Spencer;Anne I. Sperling;J. A. Bluestone
小鼠胶原诱导性关节炎（CIA）是一种由II型胶原诱导的T细胞介导的疾病。先前的研究表明，表达特定V β TCR基因的CD 4+细胞参与该模型中关节炎的诱导。在本报告中，我们证明了CD 4-，CD 8-，TCR γ δ细胞存在于关节炎关节，在患有CIA的DBA/1 lac J小鼠的外周淋巴组织中扩增，并在体外对抗TCR γ δ mAb UC 7 - 13 D5（13 D5）产生应答。为了直接研究γ δ TCR在鼠CIA中的作用，在注射II型胶原之前或之后40天，给DBA/1 lac J小鼠注射13 D5。我们的研究结果表明，与单独使用II型胶原治疗相比，在注射II型胶原前1天开始的13 D5腹腔注射显著延迟了CIA的发作和严重程度。相比之下，与注射对照仓鼠IgG或F（ab '）的关节炎小鼠相比，注射胶原蛋白40天后注射抗TCR γ δ mAb会导致严重关节炎的快速发作，并伴有骨侵蚀和炎症关节细胞浸润的增加。13 D5的2片段。注射完整13 D5的关节炎小鼠体重迅速减轻，表明13 D5可能诱导类似于注射抗CD 3后在小鼠和人中观察到的马槟榔碱介导的综合征。从关节炎小鼠胶原酶消化后分离的关节细胞的流式细胞术分析表明，13 D5注射诱导关节炎关节内CD 4-、CD 8-、PgP-1（CD 44）+细胞的积累，而注射对照仓鼠IgG的小鼠的关节炎关节含有具有CD 4+、CD 8-表型的细胞。建立表达来自关节炎小鼠的发炎关节的γ δ TCR的CD 3 + T细胞系，并通过聚合酶链反应检查V γ的使用。V γ 2重排是主要的T细胞系建立从发炎的滑膜以及新鲜分离的滑膜细胞关节炎小鼠，而滑膜细胞nonarthritic小鼠没有表现出V γ 2重排。总之，本报告中描述的结果表明，在DBA/1 lac J小鼠中，γ δ TCR T细胞在CIA的发病机制中具有直接作用。
Murine collagen-induced arthritis (CIA) is a T cell-mediated disease which is induced by injection of type II collagen. Previous studies have shown that CD4+ cells which express particular V beta TCR genes are involved in the induction of arthritis in this model. In the present report we demonstrate that CD4-, CD8-, TCR gamma delta cells are present in arthritic joints, expanded in peripheral lymphoid tissue of DBA/1 lac J mice with CIA, and respond in vitro to the anti-TCR gamma delta mAb UC7-13D5 (13D5). In order to directly investigate the role of the gamma delta TCR in murine CIA, DBA/1 lac J mice were injected with 13D5 before or 40 days after injection of type II collagen. Our results demonstrate that i.p. injections of 13D5 initiated 1 day before injection of type II collagen significantly delays both the onset and severity of CIA compared with treatment with type II collagen alone. In contrast, anti-TCR gamma delta mAb injection of arthritic mice 40 days after collagen injection resulted in the rapid onset of severe arthritis which was accompanied by increased bone erosion and cell infiltration into inflamed joints compared with arthritic mice injected with either control hamster IgG or F(ab')2 fragments of 13D5. Arthritic mice injected with intact 13D5 rapidly lost weight, suggesting that 13D5 may induce a cytokine-mediated syndrome similar to that observed in mice and humans after the injection of anti-CD3. Flow cytometry analysis of joint cells isolated after collagenase digestion from arthritic mice demonstrated that 13D5 injection induces the accumulation of CD4-, CD8-, PgP-1 (CD44)+ cells within arthritic joints, whereas arthritic joints from mice injected with control hamster IgG contained cells with a CD4+, CD8- phenotype. CD3+ T cell lines which express the gamma delta TCR from inflamed joints of arthritic mice were established and examined for V gamma usage by the polymerase chain reaction. V gamma 2 rearrangements were predominant in both T cell lines established from inflamed synovium as well as freshly isolated synovial cells from arthritic mice, whereas synovial cells from nonarthritic mice did not demonstrate V gamma 2 rearrangements. Taken together, the results described in this report suggest a direct role for gamma delta TCR T cells in the pathogenesis of CIA in DBA/1 lac J mice.