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Recipient T Cells Mediate Reperfusion Injury after Lung Transplantation in the Rat

Marc de Perrot^*, Kevin Young, Yumiko Imai^*, Mingyao Liu^*, Thomas K. Waddell^*, Stefan Fischer^*, Li Zhang and Shaf Keshavjee^1,*

^* Thoracic Surgery Research Laboratory and Departments of Laboratory Medicine, Pathobiology and Immunology, Toronto General Hospital Research Institute, University of Toronto, Toronto, Canada

Leukocytes have been implicated in ischemia-reperfusion (IR) injury of the lung, but the individual role of T cells has not been explored. Recent evidence in mice suggests that T cells may play a role in IR injury. Using a syngeneic (Lewis to Lewis) rat lung transplant model, we observed that recipient CD4⁺ T cells infiltrated lung grafts within 1 h of reperfusion and up-regulated the expression of CD25 over the ensuing 12 h. Nude rats (rnu/rnu) and heterozygous rats (rnu/+) were used to determine the role of T cells in IR injury. No significant difference in lung function was observed between nude and heterozygous recipient rats after 2 h of reperfusion. However, after 12 h of reperfusion, recipient nude rats had significantly higher oxygenation and lower peak airway pressure than recipient heterozygous rats. This was associated with significantly lower levels of IFN- in transplanted lung tissue of recipient nude rats. Reconstitution of recipient nude rats with T cells from heterozygous rats restored IR injury after 12 h of reperfusion. The effect of T cells was independent of neutrophil recruitment and activation in the transplanted lung. These results demonstrate that recipient T cells are activated and mediate IR injury during lung transplantation in rats.

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