Lentiviral vector delivery of human interleukin-7 (hIL-7) to human immune system (HIS) mice expands T lymphocyte populations.
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-/-gammac-/- mice following a single intravenous injection. hIL-7 promoted homeostatic proliferation of both adoptively transferred and endogenously generated T-cells in Rag2-/-gammac-/- 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.
O'Connell
Ryan M
RM
Division of Biology, California Institute of Technology, Pasadena, California, United States of America.
Balazs
Alejandro B
AB
Rao
Dinesh S
DS
Kivork
Christine
C
Yang
Lili
L
Baltimore
David
D
D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics* / Q000276:immunology*; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D019562:Viral Load
D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse