Human T cell development in HSC-engrafted NSG mice is dependent on age of the recipient (HEM4P.247)

Abstract

Abstract Humanized mouse models are an exciting alternative for the investigation of human hematopoiesis, immunobiology, autoimmunity, infectious diseases, cancer biology, transplantation biology and regenerative medicine. However the efficient generation of humanized mice is complicated by the availability of numerous mouse strains and the large diversity of engraftment protocols. NOD-scid IL2rγnull (NSG) mice injected with human HSC support high levels of engraftment and develop a functional human immune system including both innate and adaptive immune cells. Previous studies have shown that injection of human HSC into newborn NSG mice results in more efficient and rapid T cell development as compared to adult NSG (>6 wk) mice. Here we compared engraftment of human HSC and immune system development following intracardiac injection into irradiated newborn NSG mice or intravenous injection into irradiated 3-wk old NSG mice. Total human cell chimerism was monitored in the blood between 6 and 18 wk after transplantation. We also evaluated the development of human T cells, B cells, monocytes, NK cells, NKT cells, conventional and plasmacytoid DC. Our results show that newborn NSG mice have higher levels of T cell reconstitution at earlier time points as compared to 3-wk old NSG recipients but that the older mice achieved comparable T cell levels at later times. Together these findings show that T cell development in humanized mice occurs with slower kinetics in older NSG mice.