Both apoptosis and complement membrane attack complex deposition are major features of murine acute graft-vs.-host disease.
The parent-into-F1 mouse model (P-->F1) of acute graft-vs.-host disease (GVHD) is a useful model of human acute GVHD because it allows the study of the T cell contribution to pathology without the complicating effects of conditioning regimens. To determine the similarity of this model to human GVHD, we assessed injury in organs typically involved in human acute GVHD (skin, liver) and less typically involved organs (spleen, kidney, lung). Mice were assessed histologically at early (2 weeks), intermediate (3 months) and late (6 month) time points. Based on the emerging roles of Fas ligand killing and complement deposition in allograft rejection, we correlated the amount of tissue specific TUNEL positive apoptosis and deposition of complement (C5b-9) with histopathologic changes. Our results indicate a striking similarity histologically between acute GVHD occurring in this model and in humans following bone marrow transplant. Moreover, C5b-9 deposition and apoptotic cell accumulation were found to parallel tissue injury in major organs of acute GVHD mice, although not all organs exhibited the same kinetic pattern. These results indicate a role for both adaptive immunity and innate immunity in this model of GVHD and support its use in modeling human acute GVHD in the nonmyeloablative setting.
Department of Medicine, Division of Rheumatology and Clinical Immunology, Baltimore, MD 21201, USA.
Florin
F
Niculescu
Teodora
T
Niculescu
Phuong
P
Nguyen
Roman
R
Puliaev
John C
JC
Papadimitriou
Anthony
A
Gaspari
Horea
H
Rus
Charles S
CS
Via
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D012867:Skin / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology
D015938:Complement Membrane Attack Complex