Impaired rejection and mucosal injury of small intestinal allografts lacking the interferon-gamma receptor.
Small intestinal mucosal T cell activation results in villous atrophy and crypt hyperplasia. There is conflicting evidence as to whether a Th1 IFN-gamma response may be involved. Using a murine intestinal transplant model of T cell-mediated enteropathy we aimed to study the role of IFN-gamma on the development of villous atrophy and crypt hyperplasia. Isografts or allografts of foetal small intestine from 129SV-/- IFN-gamma receptor knockout mice or wild type mice were implanted under the kidney capsule of Balb/c recipient mice. Grafts were examined histologically at intervals from 2 to 9 days post implantation for signs of rejection. Quantitative rtPCR for IFN-gamma, TNFalpha and IL-4 was conducted on grafts at 5 and 9 days post implantation. In allografts, rejection accompanied by the development of villous atrophy and crypt hyperplasia, occurred in a time-dependent manner. However this process was markedly slower in the IFN-gamma receptor knockout grafts compared to the wild type grafts at 5 days (chi2 = 10.08, P = 0.007) and 9 days post implantation (chi2 = 13.25, P = 0.004). There were also significantly fewer TNFalpha transcripts in allografts of IFN-gamma-/- intestine than in wild type allografts (P = 0.02). IFN-gamma has a partial, but not obligatory, role in the development of villous atrophy and crypt hyperplasia during T cell mediated rejection of intestinal allografts.
Veitch
Andrew M
AM
Digestive Diseases Research Centre, St Bartholomew's and the Royal London School of Medicine and Dentistry, London UK. Dr.Veitch@rwh-tr.nhs.uk
Higgins
Lisa M
LM
Bajaj-Elliot
Mona
M
Farthing
Michael J G
MJ
MacDonald
Thomas T
TT
D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D007421:Intestine, Small / Q000196:embryology / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D013995:Time; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D015847:Interleukin-4; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor