Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation
David A. Randolph, … , Cynthia J.L. Carruthers, David D. Chaplin
David A. Randolph, … , Cynthia J.L. Carruthers, David D. Chaplin
Published October 15, 1999
Citation Information: J Clin Invest. 1999;104(8):1021-1029. https://doi.org/10.1172/JCI7631.
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Article

Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation

Abstract

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-α 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.

Authors

David A. Randolph, Robin Stephens, Cynthia J.L. Carruthers, David D. Chaplin

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Th1 cells promote recruitment of Th2 cells to the airways after the chal...
Th1 cells promote recruitment of Th2 cells to the airways after the challenge. Cultured T cells (107) were labeled with the fluorescent dyes PKH26 (red) or PKH67 (green) and transferred to recipient mice. In the morning and again in the afternoon of the next day, the mice were challenged with an aerosol of 1% OVA in sterile PBS. Three days after the challenge, lung tissue was collected and frozen. Fluorescent cells in the tissue were detected directly by fluorescence microscopy of air-dried 10-μm sections. Where indicated, eosinophils in the tissue were detected by virtue of the cyanide-resistant peroxidase activity in their granules. For detection of eosinophils, lung sections were fixed in acetone and then incubated in a DAB solution containing 1.6 mg/mL KCN. Shown are examples of lung tissue from recipients of (a) 107 PKH26-labeled Th1 cells, (b) 107 PKH26-labeled Th2 cells (c–f), 107 PKH67-labeled Th1 cells, and 107 PKH26-labeled Th2 cells. (c) Single exposure demonstrating Th1 cells. (d) Single exposure revealing Th2 cells in the same section as c. (e) Double exposure demonstrating Th1 and Th2 cells in close proximity to one another. (f) Detection of eosinophils (brown DAB staining) in the same section as e. Similar results were seen in 2 separate experiments.