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

Nat Med. 2006 Nov;12(11):1316-22. doi: 10.1038/nm1431. Epub 2006 Oct 22.

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 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Bacterial Toxins / immunology*
  • Enterotoxins / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunity, Innate*
  • Immunohistochemistry
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Superantigens / immunology*
  • T-Lymphocytes / immunology

Substances

  • Bacterial Toxins
  • Enterotoxins
  • Superantigens
  • enterotoxin F, Staphylococcal