Transfer of a functional human immune system to mice with severe combined immunodeficiency

作者: Donald E. Mosier , Richard J. Gulizia , Stephen M. Baird , Darcy B. Wilson

DOI: 10.1038/335256A0

关键词: ImmunityImmunopathologyImmunologyHumoral immunityBiologyAdoptive cell transferAntigenImmune systemSevere combined immunodeficiencyVirologyViral pathogenesis

摘要: The pressing need for a better experimental system AIDS research has brought into sharp focus the shortcomings of available animal models and practical ethical limitations studies immune responses viral pathogenesis in humans. Current human are limited to relatively restrictive vivo experiments several vitro systems that, although useful, allow only short-term support few antigens. Neither model is particularly amenable diseases system. We report here that injection peripheral blood leukocytes (PBL) can result stable long-term reconstitution functional mice with severe combined immunodeficiency (SCID). Human PBL transplanted SCID increase number survive at least six months; reconstituted show spontaneous secretion immunoglobulin specific antibody response induced following immunization tetanus toxoid. All major cell populations present found lymphoid tissue recipients, relative proportions B cells, T-cell subsets monocytes/macrophages recipients differ from those normal and, 50 x 10(6) or more Epstein-Barr virus (EBV)-seropositive donors, EBV-positive B-cell lymphomas often develop. Our results suggest xenogeneic transplantation cells may provide useful study function, pathogenic agents early events lymphomagensis.

参考文章(11)
Peter Newmark, Receding hopes of AIDS vaccines. Nature. ,vol. 333, pp. 699- 699 ,(1988) , 10.1038/333699A0
H. Takita, R. B. Bankert, S. Reddy, D. Piccione, Human Lung Tumor Growth Established in the Lung and Subcutaneous Tissue of Mice with Severe Combined Immunodeficiency Cancer Research. ,vol. 47, pp. 2456- 2460 ,(1987)
Daniel Zagury, Jacky Bernard, Remi Cheynier, Isabelle Desportes, Regine Leonard, Michelle Fouchard, Brigitte Reveil, Daniele Ittele, Zirimwabagangabo Lurhuma, Kalumbu Mbayo, Justin Wane, Jean-Jacques Salaun, Bernard Goussard, Loic Dechazal, Arsene Burny, Peter Nara, Robert C Gallo, A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS Nature. ,vol. 332, pp. 728- 731 ,(1988) , 10.1038/332728A0
Z. Farzad, K. James, D.B.L. McClelland, Measurement of human and mouse anti-tetanus antibodies and isotype analysis by ELISA. Journal of Immunological Methods. ,vol. 87, pp. 119- 125 ,(1986) , 10.1016/0022-1759(86)90351-0
Gayle C. Bosma, R. Philip Custer, Melvin J. Bosma, A severe combined immunodeficiency mutation in the mouse Nature. ,vol. 301, pp. 527- 530 ,(1983) , 10.1038/301527A0
G Tosato, A D Steinberg, R Yarchoan, C A Heilman, S E Pike, V De Seau, R M Blaese, Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis. Journal of Clinical Investigation. ,vol. 73, pp. 1789- 1795 ,(1984) , 10.1172/JCI111388
P Aman, B Ehlin-Henriksson, G Klein, Epstein-Barr virus susceptibility of normal human B lymphocyte populations. Journal of Experimental Medicine. ,vol. 159, pp. 208- 220 ,(1984) , 10.1084/JEM.159.1.208
Raif S. Geha, Regulation of human B cell activation. Immunological Reviews. ,vol. 45, pp. 275- 305 ,(1979) , 10.1111/J.1600-065X.1979.TB00281.X