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

Michael W. Melkus, Jacob D. Estes, Angela Padgett-Thomas, Joel Gatlin, Paul W. Denton, Florence A. Othieno, Anja K. Wege, Ashley T. Haase, J. Victor Garcia

Research output: Contribution to journalArticle

420 Scopus citations

Abstract

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 Vβ2 + 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.

Original languageEnglish (US)
Pages (from-to)1316-1322
Number of pages7
JournalNature medicine
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2006

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Melkus, M. W., Estes, J. D., Padgett-Thomas, A., Gatlin, J., Denton, P. W., Othieno, F. A., Wege, A. K., Haase, A. T., & Garcia, J. V. (2006). Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nature medicine, 12(11), 1316-1322. https://doi.org/10.1038/nm1431