Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1.
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.
Melkus
Michael W
MW
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
Estes
Jacob D
JD
Padgett-Thomas
Angela
A
Gatlin
Joel
J
Denton
Paul W
PW
Othieno
Florence A
FA
Wege
Anja K
AK
Haase
Ashley T
AT
Garcia
J Victor
JV
D000222:Adaptation, Physiological; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D001427:Bacterial Toxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal