Enhanced T cell cytokine gene expression in mouse airway obliterative bronchiolitis

被引:43
作者
Neuringer, IP
Walsh, SP
Mannon, RB
Gabriel, S
Aris, RM
机构
[1] Univ N Carolina, Dept Pulm Crit Care Med, Chapel Hill, NC USA
[2] Univ N Carolina, Cyst Fibrosis Res & Treatment Ctr, Chapel Hill, NC USA
[3] Univ N Carolina, Dept Med, Dept Nephrol, Chapel Hill, NC 27599 USA
[4] Durham VA Med Ctr, Chapel Hill, NC 27599 USA
关键词
D O I
10.1097/00007890-200002150-00016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Obliterative bronchiolitis (OB), chronic allograft rejection of the lung, is a major cause of morbidity and mortality after lung transplantation. Previous studies using the heterotopic mouse trachea model of chronic airway rejection have shown a T cell infiltrate composed of CD4(+) and CD8(+) T cells. The goal of these experiments was to characterize the pattern of T lymphocyte cytokines during chronic airway rejection using the heterotopic mouse trachea model. Methods. Isografts (BALB/c into BALB/c) and allografts (BALB/c into C57BL/6) were implanted into cyclosporin-treated animals and harvested 2, 4, 6, and 10 weeks posttransplant. Cytokine mRNA expression in these grafts was determined using reverse transcription polymerase chain reactions. Expression of Th1 cytokines, interleukin- (IL) 2 and gamma-interferon, and Th2 cytokines, IL-4, and IL-10 were analyzed, as well as the cytotoxic lymphocyte product granzyme B and expressed relative to p-actin gene expression. Results. In allografts, expression of IL-2 (P=0.002), gamma-interferon (P=2x10(-6)), granzyme B (P=0.003). IL-4 (P=0.06), and IL-IO (P=8x10(-6)) were 2- to 10-fold higher compared to isografts throughout the timecourse of graft injury. Th1 and cytotoxic lymphocyte gene expression were increased to a greater extent than Th2 cytokines in allografts compared with isografts, and both Th1 and Th2 cytokine gene expression persisted at 6-10 weeks. Conclusions. These data suggest that Th1, Th2, and cytotoxic lymphocyte subtypes all contribute to the development of obliterative bronchiolitis in the heterotopic mouse trachea model, Efforts to reduce the development of obliterative bronchiolitis may require the antagonism of multiple T cell pathways.
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收藏
页码:399 / 405
页数:7
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