This contract proposes to develop, optimize, and test the production of HIS mice using hematopoietic stem cells from cord blood, including the co-transplantation of neonatal thymic tissue. Comprehensive characterizations of the adaptive and innate human immune systems will include testing its ability to respond to a standard human vaccination and an allograft. The chosen models for optimization and improvement center on increasing populations of innate lymphoid cells which facilitate lymphoid tissue development, that in turn would lead to more robust and complete development of the human immune system.