Recipient T cells mediate reperfusion injury after lung transplantation in the rat.
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-gamma 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.
de Perrot
Marc
M
Thoracic Surgery Research Laboratory and Department of Laboratory Medicine, Toronto General Hospital Research Institute, University of Toronto, Toronto, Canada.
Young
Kevin
K
Imai
Yumiko
Y
Liu
Mingyao
M
Waddell
Thomas K
TK
Fischer
Stefan
S
Zhang
Li
L
Keshavjee
Shaf
S
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007511:Ischemia / Q000276:immunology / Q000473:pathology; D007700:Kinetics; D008168:Lung / Q000098:blood supply; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology*; D008297:Male; D018375:Neutrophil Activation / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D013997:Time Factors
D015375:Receptors, Interleukin-2; D007371:Interferon-gamma