Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1

• Published in: Nature medicine Vol. 12; no. 11; pp. 1316 - 1322
• Main Authors: Garcia, J Victor, Melkus, Michael W, Estes, Jacob D, Padgett-Thomas, Angela, Gatlin, Joel, Denton, Paul W, Othieno, Florence A, Wege, Anja K, Haase, Ashley T
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-11-2006
• Subjects: Adaptation, Physiological; Animals; Bacterial Toxins - immunology; Cytokines; Enterotoxins - immunology; Enzyme-Linked Immunosorbent Assay; Epstein-Barr virus; Herpesvirus 4, Human - immunology; Humans; Immune response; Immunity, Innate; Immunohistochemistry; Immunology; Infections; Leukocytes; Liver; Mice; Mice, Inbred NOD; Mice, SCID; Repopulation; Rodents; Superantigens - immunology; T-Lymphocytes - immunology; Toxins
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm1431

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 Vbeta2+ 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.