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

Michael W. Melkus, Jacob 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

404 Citations (Scopus)

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
Externally publishedYes

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T-cells
Adaptive Immunity
Human Herpesvirus 4
Viruses
Innate Immunity
Superantigens
Liver
Dendritic Cells
T-Lymphocytes
Macrophages
Demonstrations
Chemical activation
Cells
Staphylococcal enterotoxin F
Tissue
Cytokines
Inbred NOD Mouse
Epstein-Barr Virus Infections
SCID Mice
Autologous Transplantation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Melkus, M. W., Estes, J., Padgett-Thomas, A., Gatlin, J., Denton, P. W., Othieno, F. A., ... 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

Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. / Melkus, Michael W.; Estes, Jacob; Padgett-Thomas, Angela; Gatlin, Joel; Denton, Paul W.; Othieno, Florence A.; Wege, Anja K.; Haase, Ashley T.; Garcia, J. Victor.

In: Nature Medicine, Vol. 12, No. 11, 01.11.2006, p. 1316-1322.

Research output: Contribution to journalArticle

Melkus, MW, Estes, J, Padgett-Thomas, A, Gatlin, J, Denton, PW, Othieno, FA, Wege, AK, Haase, AT & Garcia, JV 2006, 'Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1', Nature Medicine, vol. 12, no. 11, pp. 1316-1322. https://doi.org/10.1038/nm1431
Melkus MW, Estes J, Padgett-Thomas A, Gatlin J, Denton PW, Othieno FA et al. Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nature Medicine. 2006 Nov 1;12(11):1316-1322. https://doi.org/10.1038/nm1431
Melkus, Michael W. ; Estes, Jacob ; Padgett-Thomas, Angela ; Gatlin, Joel ; Denton, Paul W. ; Othieno, Florence A. ; Wege, Anja K. ; Haase, Ashley T. ; Garcia, J. Victor. / Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. In: Nature Medicine. 2006 ; Vol. 12, No. 11. pp. 1316-1322.
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