Lentiviral Vector Delivery of Human Interleukin-7 (hIL-7) to Human Immune System (HIS) Mice Expands T Lymphocyte Populations

被引：45

作者：

O'Connell, Ryan M. ^{[1
]}

Balazs, Alejandro B. ^{[1
]}

Rao, Dinesh S. ^{[1
,2
]}

Kivork, Christine ^{[1
]}

Yang, Lili ^{[1
]}

Baltimore, David ^{[1
]}

机构：

[1] CALTECH, Div Biol, Pasadena, CA 91125 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

来源：

PLOS ONE | 2010年 / 5卷 / 08期

关键词：

HEMATOPOIETIC STEM-CELLS; IN-VIVO; GENE DELIVERY; SCID MICE; IL-7; HOMEOSTASIS; BLOOD; NAIVE; PROLIFERATION; TRANSDUCTION;

D O I：

10.1371/journal.pone.0012009

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genetically modified mice carrying engrafted human tissues provide useful models to study human cell biology in physiologically relevant contexts. However, there remain several obstacles limiting the compatibility of human cells within their mouse hosts. Among these is inadequate cross-reactvitiy between certain mouse cytokines and human cellular receptors, depriving the graft of important survival and growth signals. To circumvent this problem, we utilized a lentivirus-based delivery system to express physiologically relevant levels of human interleukin-7 (hIL-7) in Rag2-/-gamma c-/-mice following a single intravenous injection. hIL-7 promoted homeostatic proliferation of both adoptively transferred and endogenously generated T-cells in Rag2-/-gamma c-/-Human Immune System (HIS) mice. Interestingly, we found that hIL-7 increased T lymphocyte numbers in the spleens of HIV infected HIS mice without affecting viral load. Taken together, our study unveils a versatile approach to deliver human cytokines to HIS mice, to both improve engraftment and determine the impact of cytokines on human diseases.

引用

页数：11

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