Reconstitution of huPBL-NSG Mice with Donor-Matched Dendritic Cells Enables Antigen-Specific T-cell Activation
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- 作者：Airi Harui (1)
Sylvia M. Kiertscher (1)
Michael D. Roth (1) (3) - 关键词：dendritic cell ; adenovirus ; vaccination ; xenotransplant ; cytokine ; humanized mouse
- 刊名：Journal of Neuroimmune Pharmacology
- 出版年：2011
- 出版时间：March 2011
- 年：2011
- 卷：6
- 期：1
- 页码：148-157
- 全文大小：347KB
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Sylvia M. Kiertscher (1)
Michael D. Roth (1) (3)
1. Division of Pulmonary & Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1690, USA
3. Division of Pulmonary & Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1690, USA - ISSN：1557-1904
文摘
Humanized mouse models provide a unique opportunity to study human immune cells in vivo, but traditional models have been limited to the evaluation of non-specific T-cell interactions due to the absence of antigen-presenting cells. In this study, immunodeficient NOD/SCID/IL2r-γnull (NSG) mice were engrafted with human peripheral blood lymphocytes alone or in combination with donor-matched monocyte-derived dendritic cells (DC) to determine whether antigen-specific T-cell activation could be reconstituted. Over a period of 3?weeks, transferred peripheral blood lymphocytes reconstituted the spleen and peripheral blood of recipient mice with predominantly human CD45-positive lymphocytes. Animals exhibited a relatively normal CD4/CD8 ratio (average 1.63:1) as well as reconstitution of CD3/CD56 (averaging 17.8%) and CD20 subsets (averaging 4.0%). Animals reconstituted with donor-matched CD11c+ DC also demonstrated a CD11c+ population within their spleen, representing 0.27% to 0.43% of the recovered human cells with concurrent expression of HLA-DR, CD40, and CD86. When immunized with adenovirus, either as free replication-incompetent vector (AdV) or as vector-transduced DC (DC/AdV), there was activation and expansion of AdV-specific T-cells, an increase in Th1 cytokines in serum, and skewing of T-cells toward an effector/memory phenotype. T-cells recovered from animals challenged with AdV in vivo proliferated and secreted a Th1-profile of cytokines in response to DC/AdV challenge in vitro. Our results suggest that engrafting NSG mice with a combination of lymphocytes and donor-matched DC can reconstitute antigen responsiveness and allow the in vivo assessment of human immune response to viruses, vaccines, and other immune challenges.