Nature Medicine
- 12, 1316 - 1322 (2006)
Published online: 22 October 2006; | doi:10.1038/nm1431
Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1Michael W Melkus1, Jacob D Estes2, Angela Padgett-Thomas1, Joel Gatlin3, Paul W Denton1, Florence A Othieno1, Anja K Wege1, Ashley T Haase2 & J Victor Garcia11
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA. 2
Department of Microbiology, Medical School, University of Minnesota, MMC 196, 420 Delaware Street S.E., Minneapolis, Minnesota 55455, USA. 3
Arena Pharmaceuticals Inc., 6161 Nancy Ridge Drive, San Diego, California 92121, USA.
Correspondence should be addressed to J Victor Garcia victor.garcia@utsouthwestern.edu Here we show that transplantation of autologous human hematopoietic fetal liver CD34+ cells into NOD/SCID mice previously implanted with human fetal thymic and liver tissues results in long-term, systemic human T-cell homeostasis. In addition, these mice show systemic repopulation with human B cells, monocytes and macrophages, and dendritic cells (DCs). T cells in these mice generate human major histocompatibility complex class I– and class II–restricted adaptive immune responses to Epstein-Barr virus (EBV) infection and are activated by human DCs to mount a potent T-cell immune response to superantigens. Administration of the superantigen toxic shock syndrome toxin 1 (TSST-1) results in the specific systemic expansion of human V 2+ T cells, release of human proinflammatory cytokines and localized, specific activation and maturation of human CD11c+ dendritic cells. This represents the first demonstration of long-term systemic human T-cell reconstitution in vivo allowing for the manifestation of the differential response by human DCs to TSST-1.
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