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Titolo:
CORRECTION OR TRANSFER OF IMMUNODEFICIENCY DUE TO TNF-LT-ALPHA DELETION BY BONE-MARROW TRANSPLANTATION
Autore:
MULLER M; EUGSTER HP; LEHIR M; SHAKHOV A; DIPADOVA F; MAURER C; QUESNIAUX VFJ; RYFFEL B;
Indirizzi:
UNIV BASEL,INST PATHOL,SCHONBEINSTR 40 CH-4003 BASEL SWITZERLAND UNIV BASEL,INST PATHOL CH-4003 BASEL SWITZERLAND UNIV ZURICH,INST TOXICOL ZURICH SWITZERLAND SANDOZ PHARMA AG,PRECLIN RES CH-4002 BASEL SWITZERLAND
Titolo Testata:
Molecular medicine
fascicolo: 2, volume: 2, anno: 1996,
pagine: 247 - 255
SICI:
1076-1551(1996)2:2<247:COTOID>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; MOLECULAR-CLONING; FACTOR RECEPTOR; EXPRESSION; HOMOLOGY; LIGAND; FAMILY; MICE; MONOCYTOGENES; LYMPHOTOXIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
M. Muller et al., "CORRECTION OR TRANSFER OF IMMUNODEFICIENCY DUE TO TNF-LT-ALPHA DELETION BY BONE-MARROW TRANSPLANTATION", Molecular medicine, 2(2), 1996, pp. 247-255

Abstract

Background: Mice with inactivated tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) genes have profound abnormalities of the immune system including lymphocytosis, lack of lymph nodes, undifferentiated spleen, hypoimmunoglobulinaemia, and defective Ig class switch. Here, we asked whether this phenotype is due to incompetent lymphohemopoietic progenitors or to a defective environment. Materials and Methods: Lethally irradiated TNF-LT alpha-deficient and wild-type mice received bone marrow cells from either TNF-LT alpha-deficient or wild-type mice. The reconstitution and transfer of the phenotype was followed by morphological and functional analyses. Results: Bone marrow cells fromwild-type mice restored the synthesis of TNF and LT alpha, corrected the splenic microarchitecture, normalized the lymphocyte counts in thecirculation, and repopulated the lamina propria with IgA-producing plasma cells of TNF-LT alpha-deficient mice. Furthermore, the formation of germinal centers in the spleen and the defective Ig class switch inresponse to a T-cell dependent antigen was corrected, while no lymph nodes were formed. Conversely, the TNF-LT alpha phenotype could be transferred to wild-type mice by bone marrow transplantation after lethalirradiation. Conclusions: These data demonstrate that most TNF and LTalpha-producing cells are bone marrow derived and radiosensitive, andthat the immunodeficiency due to TNF-LT alpha deletion can be corrected to a large extent by normal bone marrow cell transplantation The genotype of the donor bone marrow cells determines the functional and structural phenotype of the TNF-LT alpha-deficient adult murine host, with the exception of lymph node formation. These findings may have therapeutic implications for the restoration of genetically defined immunodeficiencies in humans.

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Documento generato il 27/01/21 alle ore 01:54:37