Cutting edge: lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous.
Mice deficient for the expression of CTLA-4 develop a lethal lymphoproliferative syndrome and multiorgan inflammation leading to death at about 4 wk of age. Here we show that RAG2-deficient mice reconstituted with CTLA-4-deficient bone marrow do not develop a lymphoproliferative syndrome despite lymphocyte infiltration mainly into pericardium and liver. Moreover, RAG2-deficient mice reconstituted with a mixture of normal and CTLA-4-deficient bone marrow remain healthy and do not develop any disease. Thus, the lethal disease observed in CTLA-4-deficient mice is not T cell autonomous and can be prevented by factors produced by normal T cells.
Basel Institute for Immunology, Switzerland.
M F
MF
Bachmann
G
G
Köhler
B
B
Ecabert
T W
TW
Mak
M
M
Kopf
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D060908:CTLA-4 Antigen; D002465:Cell Movement / Q000276:immunology; D018796:Immunoconjugates; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010496:Pericardium / Q000276:immunology / Q000473:pathology; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D000069594:Abatacept