Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants.
Immunity to collagen V [col(V)] contributes to lung 'rejection.' We hypothesized that ischemia reperfusion injury (IRI) associated with lung transplantation unmasks antigenic col(V) such that fresh and well-healed lung grafts have differential susceptibility to anti-col(V)-mediated injury; and expression of the autoimmune cytokines, IL-17 and IL-23, are associated with this process. Adoptive transfer of col(V)-reactive lymphocytes to WKY rats induced grade 2 rejection in fresh isografts, but induced worse pathology (grade 3) when transferred to isograft recipients 30 days post-transplantation. Immunhistochemistry detected col(V) in fresh and well-healed isografts but not native lungs. Hen egg lysozyme-reactive lymphocytes (HEL, control) did not induce lung disease in any group. Col(V), but not HEL, immunization induced transcripts for IL-17 and IL-23 (p19) in the cells utilized for adoptive transfer. Transcripts for IL-17 were upregulated in fresh, but not well-healed isografts after transfer of col(V)-reactive cells. These data show that IRI predisposes to anti-col(V)-mediated pathology; col(V)-reactive lymphocytes express IL-17 and IL-23; and anti-col(V)-mediated lung disease is associated with local expression of IL-17. Finally, because of similar histologic patterns, the pathology of clinical rejection may reflect the activity of autoimmunity to col(V) and/or alloimmunity.
Center for Immunobiology, Indiana University of School of Medicine, Indianapolis, IN, USA.
S
S
Yoshida
A
A
Haque
T
T
Mizobuchi
T
T
Iwata
M
M
Chiyo
T J
TJ
Webb
L A
LA
Baldridge
K M
KM
Heidler
O W
OW
Cummings
T
T
Fujisawa
J S
JS
Blum
D D
DD
Brand
D S
DS
Wilkes
D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D024062:Collagen Type V / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D020381:Interleukin-17 / Q000235:genetics*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics*; D008168:Lung / Q000276:immunology / Q000473:pathology*; D016040:Lung Transplantation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000276:immunology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D024062:Collagen Type V; C508842:Il23a protein, rat; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins