Correction of the TNF-LT alpha-deficient phenotype by bone marrow transplantation.
Mice with inactivated TNF-LT alpha genes have profound abnormalities of the immune system with hypoimmunoglobulinaemia, lack of lymph nodes, undifferentiated spleen, and defective Ig class switch. Transplantation of bone marrow cells from wild-type mice restored the synthesis of TNF, corrected the splenic microarchitecture, repopulated the lamina propria with IgA-producing plasma cells, and normalized the serum immunoglobulin levels of TNF-LT alpha deficient mice. Furthermore, the formation of germinal centers in the spleen and the defective Ig class switch in response to a T-cell-dependent antigen is corrected. These data demonstrate that most TNF-producing cells are bone-marrow-derived, and that the immunodeficiency due to TNF-LT alpha deletion can be corrected to a large extent by normal bone marrow, cell transplantation.
Ryffel
B
B
Institute of Pathology, University of Basel, Switzerland.
Le Hir
M
M
Müller
M
M
Eugster
H P
HP
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation; D005455:Fluorescent Antibody Technique; D018858:Germinal Center / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha