Randolph D A, Stephens R, Carruthers C J, Chaplin D D
Division of Allergy and Immunology, Department of Internal Medicine and Center for Immunology, and Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Clin Invest. 1999 Oct;104(8):1021-9. doi: 10.1172/JCI7631.
We have studied the actions of helper T lymphocyte-1 and -2 (Th1 and Th2) cells in an acute model of eosinophilic airway inflammation by infusing chicken ovalbumin-specific (OVA-specific) Th1 cells, Th2 cells, or both into unsensitized mice and challenging the mice with an OVA aerosol. OVA challenge after infusion of Th1 cells alone resulted in airway inflammation with lymphocytes and monocytes. Challenge after the infusion of Th2 cells alone resulted in minimal inflammation. In contrast, when Th1 and Th2 cells were transferred together, they cooperated to promote a robust eosinophil-predominant inflammatory response. Th1 cells alone were readily recruited to the airways after challenge, but in the absence of Th1 cells, Th2 cells did not accumulate in the airways. When transferred together, both Th1 and Th2 cells, as well as endogenous eosinophils, were effectively recruited. This recruitment was correlated with increased VCAM-1 expression in the medium- and large-sized vessels of the lung and could be inhibited by treating the mice with neutralizing antibodies to TNF-alpha or VCAM-1. These data indicate that Th2 cells require signals in addition to antigen for their effective recruitment to the airways. Th1 cells can provide these signals.
我们通过向未致敏小鼠输注鸡卵清蛋白特异性(OVA特异性)辅助性T淋巴细胞1型和2型(Th1和Th2)细胞,并用OVA气雾剂激发小鼠,在嗜酸性气道炎症的急性模型中研究了Th1和Th2细胞的作用。单独输注Th1细胞后用OVA激发导致气道出现淋巴细胞和单核细胞炎症。单独输注Th2细胞后激发导致炎症轻微。相比之下,当Th1和Th2细胞一起转移时,它们协同促进强烈的以嗜酸性粒细胞为主的炎症反应。单独的Th1细胞在激发后很容易被募集到气道,但在没有Th1细胞的情况下,Th2细胞不会在气道中积聚。当一起转移时,Th1和Th2细胞以及内源性嗜酸性粒细胞都能被有效募集。这种募集与肺中、大血管中VCAM-1表达增加相关,并且可以通过用抗TNF-α或VCAM-1中和抗体处理小鼠来抑制。这些数据表明,Th2细胞除了抗原外还需要信号才能有效募集到气道。Th1细胞可以提供这些信号。