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CD4+ T淋巴细胞对黏膜反应的调节:抗L3T4治疗对胃肠道免疫系统的影响。

Regulation of mucosal responses by CD4+ T lymphocytes: effects of anti-L3T4 treatment on the gastrointestinal immune system.

作者信息

Mega J, Bruce M G, Beagley K W, McGhee J R, Taguchi T, Pitts A M, McGhee M L, Bucy R P, Eldridge J H, Mestecky J

机构信息

Department of Oral Biology, University of Alabama, Birmingham 35294.

出版信息

Int Immunol. 1991 Aug;3(8):793-805. doi: 10.1093/intimm/3.8.793.

DOI:10.1093/intimm/3.8.793
PMID:1680381
Abstract

The role of CD4+ T cells in the gastrointestinal (GI) immune system in vivo was studied in mice selectively depleted of this subset by treatment with monoclonal anti-L3T4 (GK1.5) mAb. Treatment of young BALB/c mice with weekly injections of anti-L3T4 mAb resulted in a selective depletion of CD4+ T cells in both IgA effector (lamina propria regions of the intestine; LP) and inductive (Peyer's patch; PP) sites. However, levels of CD3+CD4-CD8+ and CD4-CD8- (double negative) T cells remained constant or increased. When sections of small intestine were assessed for the isotype of Ig-containing cells, normal mice contained predominantly IgA plasma cells with small numbers of IgM and IgG plasma cells while anti-L3T4 treatment dramatically reduced the numbers of IgA plasma cells. When numbers of IgA-producing cells were assessed by the isotype-specific ELISPOT assay, the LPL of anti-L3T4 mAb-treated mice showed an 80% reduction in the number of IgA spot-forming cells. The effect of anti-L3T4 mAb treatment on IgA inductive sites was also studied and this treatment reduced the overall size of PP as well as the germinal centers in this tissue. Although anti-L3T4 treatment depleted CD3+CD4+ T cells in PP, the relative frequency of surface IgA-positive (slgA+) B cells in this tissue did not change. These results show that repeated injection of anti-L3T4 mAb results in a CD4+ T cell deficiency in both IgA inductive (PP) and effector (LP) sites. The depletion of CD4+ T cells resulted in reductions in the numbers of mature IgA plasma cells present in the LP of gut-associated tissues, and reduced the overall size of PP including germinal centers, but did not affect the frequency of sIgA+ B cells in this IgA inductive site.

摘要

通过用单克隆抗L3T4(GK1.5)单克隆抗体处理,选择性清除该亚群的小鼠,研究了CD4 + T细胞在体内胃肠道(GI)免疫系统中的作用。每周注射抗L3T4单克隆抗体处理年轻的BALB / c小鼠,导致IgA效应部位(肠道固有层区域;LP)和诱导部位(派尔集合淋巴结;PP)中的CD4 + T细胞选择性减少。然而,CD3 + CD4 - CD8 +和CD4 - CD8 - (双阴性)T细胞水平保持恒定或增加。当评估小肠切片中含Ig细胞的同种型时,正常小鼠主要含有IgA浆细胞,少量IgM和IgG浆细胞,而抗L3T4处理显著减少了IgA浆细胞的数量。当通过同种型特异性ELISPOT测定评估产生IgA的细胞数量时,抗L3T4单克隆抗体处理的小鼠的LPL显示IgA斑点形成细胞数量减少了80%。还研究了抗L3T4单克隆抗体处理对IgA诱导部位的影响,这种处理减少了PP的整体大小以及该组织中的生发中心。尽管抗L3T4处理使PP中的CD3 + CD4 + T细胞减少,但该组织中表面IgA阳性(slgA +)B细胞的相对频率没有变化。这些结果表明,重复注射抗L3T4单克隆抗体导致IgA诱导部位(PP)和效应部位(LP)均出现CD4 + T细胞缺乏。CD4 + T细胞的减少导致肠道相关组织LP中成熟IgA浆细胞数量减少,并减小了包括生发中心在内的PP的整体大小,但不影响该IgA诱导部位中sIgA + B细胞的频率。

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