Regulation of human cell engraftment and development of EBV-related lymphoproliferative disorders in Hu-PBL-scid mice - PubMed (original) (raw)
Regulation of human cell engraftment and development of EBV-related lymphoproliferative disorders in Hu-PBL-scid mice
E J Wagar et al. J Immunol. 2000.
Abstract
Human PBMC engraft in mice homozygous for the severe combined immunodeficiency (Prkdcscid) mutation (Hu-PBL-scid mice). Hu-PBL-NOD-scid mice generate 5- to 10-fold higher levels of human cells than do Hu-PBL-C.B-17-scid mice, and Hu-PBL-NOD-scid beta2-microglobulin-null (NOD-scid-B2mnull) mice support even higher levels of engraftment, particularly CD4+ T cells. The basis for increased engraftment of human PBMC and the functional capabilities of these cells in NOD-scid and NOD-scid-B2mnull mice are unknown. We now report that human cell proliferation in NOD-scid mice increased after in vivo depletion of NK cells. Human cell engraftment depended on CD4+ cells and required CD40-CD154 interaction, but engrafted CD4+ cells rapidly became nonresponsive to anti-CD3 Ab stimulation. Depletion of human CD8+ cells led to increased human CD4+ and CD20+ cell engraftment and increased levels of human Ig. We further document that Hu-PBL-NOD-scid mice are resistant to development of human EBV-related lymphoproliferative disorders. These disorders, however, develop rapidly following depletion of human CD8+ cells and are prevented by re-engraftment of CD8+ T cells. These data demonstrate that 1) murine NK cells regulate human cell engraftment in scid recipients; 2) human CD4+ cells are required for human CD8+ cell engraftment; and 3) once engrafted, human CD8+ cells regulate human CD4+ and CD20+ cell expansion, Ig levels, and outgrowth of EBV-related lymphoproliferative disorders. We propose that the Hu-PBL-NOD-scid model is suitable for the in vivo analysis of immunoregulatory interactions between human CD4+ and CD8+ cells.
Similar articles
- Alloimmune injury and rejection of human skin grafts on human peripheral blood lymphocyte-reconstituted non-obese diabetic severe combined immunodeficient beta2-microglobulin-null mice.
Turgeon NA, Banuelos SJ, Shultz LD, Lyons BL, Iwakoshi N, Greiner DL, Mordes JP, Rossini AA, Appel MC. Turgeon NA, et al. Exp Biol Med (Maywood). 2003 Oct;228(9):1096-104. doi: 10.1177/153537020322800918. Exp Biol Med (Maywood). 2003. PMID: 14530522 - Human peripheral blood leukocyte engraftment into SCID mice: critical role of CD4(+) T cells.
Duchosal MA, Mauray S, Rüegg M, Trouillet P, Vallet V, Aarden L, Tissot JD, Schapira M. Duchosal MA, et al. Cell Immunol. 2001 Jul 10;211(1):8-20. doi: 10.1006/cimm.2001.1822. Cell Immunol. 2001. PMID: 11585383 - A novel mouse xenotransplantation model of EBV-T/NK-LPD and the application of the mouse model.
Imadome K. Imadome K. Nihon Rinsho Meneki Gakkai Kaishi. 2013;36(6):433-41. doi: 10.2177/jsci.36.433. Nihon Rinsho Meneki Gakkai Kaishi. 2013. PMID: 24390103 Review. - The role of virus-specific CD4+ T cells in the control of Epstein-Barr virus infection.
Mautner J, Bornkamm GW. Mautner J, et al. Eur J Cell Biol. 2012 Jan;91(1):31-5. doi: 10.1016/j.ejcb.2011.01.007. Epub 2011 Apr 1. Eur J Cell Biol. 2012. PMID: 21458882 Review.
Cited by
- Use of Hu-PBL Mice to Study Pathogenesis of Human-Restricted Viruses.
Brunetti JE, Kitsera M, Muñoz-Fontela C, Rodríguez E. Brunetti JE, et al. Viruses. 2023 Jan 13;15(1):228. doi: 10.3390/v15010228. Viruses. 2023. PMID: 36680271 Free PMC article. Review. - An improved cell line-derived xenograft humanized mouse model for evaluation of PD-1/PD-L1 blocker BMS202-induced immune responses in colorectal cancer.
Shang P, Yu L, Cao S, Guo C, Zhang W. Shang P, et al. Acta Biochim Biophys Sin (Shanghai). 2022 Oct 25;54(10):1497-1506. doi: 10.3724/abbs.2022145. Acta Biochim Biophys Sin (Shanghai). 2022. PMID: 36269133 Free PMC article. - Modeling human T1D-associated autoimmune processes.
Khosravi-Maharlooei M, Madley R, Borsotti C, Ferreira LMR, Sharp RC, Brehm MA, Greiner DL, Parent AV, Anderson MS, Sykes M, Creusot RJ. Khosravi-Maharlooei M, et al. Mol Metab. 2022 Feb;56:101417. doi: 10.1016/j.molmet.2021.101417. Epub 2021 Dec 10. Mol Metab. 2022. PMID: 34902607 Free PMC article. Review. - Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research.
Radaelli E, Santagostino SF, Sellers RS, Brayton CF. Radaelli E, et al. ILAR J. 2018 Dec 31;59(3):211-246. doi: 10.1093/ilar/ily026. ILAR J. 2018. PMID: 31197363 Free PMC article. Review. - Development of Severe Combined Immunodeficient (SCID) Pig Models for Translational Cancer Modeling: Future Insights on How Humanized SCID Pigs Can Improve Preclinical Cancer Research.
Boettcher AN, Loving CL, Cunnick JE, Tuggle CK. Boettcher AN, et al. Front Oncol. 2018 Nov 30;8:559. doi: 10.3389/fonc.2018.00559. eCollection 2018. Front Oncol. 2018. PMID: 30560086 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials