NK Cell Development in Human Immune System (HIS) Mice and Their Role in HIV Pathogenesis

Abstract

Studies on mouse natural killer (NK) cells reveal their major role in host innate immunity against viral pathogens and tumor cells. In recent years, there has been a growing interest to develop therapeutics and prophylactics for human immunodeficiency virus (HIV) infection by targeting human NK cells. These novel approaches require advanced knowledge of human NK cell development and function. Due to the limited access to human tissue samples, the studies of human NK cells are generally restricted to in vitro analysis of NK cells from peripheral blood. Hence, the recent development of a small animal model with stable human hematopoiesis has provided a powerful tool to study human immune responses in vivo. Human NK cell reconstitution in human immune system (HIS) mice can be significantly boosted by exogenous human cytokines resulting in a pertinent model to study the role for NK cells in regulating HIV-induced pathology. In present chapter, we review some aspects of NK cell biology and the role of NK cells in HIV infection, and discuss the human NK cell engraftment in current HIS mouse models and possibilities to use HIS mice to study human NK cell during the course of HIV infection.