A two-phase pathogenesis of graft-versus-host disease in mice.
Activation of donor T cells is required for the development of graft-versus-host disease (GVHD), a major complication of bone marrow transplantation. We investigated a murine model of GVHD across major and minor histocompatibility barriers. BALB/c recipients were lethally irradiated and transplanted with 10(7) bone marrow and 5 x 10(6) spleen cells from C57BL/6 donors. There were two separate phases of clinical disease. The first phase was most severe on day 7 after transplant. Weight and condition improved until day 12 and then a second phase of clinical GVHD commenced, which persisted until euthanasia. IL-2 mRNA expression, as a measure of T cell activation, was determined by quantitative PCR. The two phases of clinical GVHD were preceded by two separate peaks of IL-2 mRNA in the spleen. Host MHC class II(+) cells became undetectable by flow cytometry 7 days after transplantation, whereas donor MHC class II(+) cells increased during the first 9 days after transplantation. Removal of donor MHC class II(+) cells from the graft had no effect on the first phase. Possible roles for host and donor antigen-presenting cells (APC) in the two phases of the disease are discussed.
van Leeuwen
L
L
Department of Haematology, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
Guiffre
A
A
Atkinson
K
K
Rainer
S P
SP
Sewell
W A
WA
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D015431:Weight Loss
D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D012333:RNA, Messenger