Cytokine Species-Specificity and Humanized Mice

Abstract

Humanized mice are immunodeficient mice in which human primary haematopoietic cells and tissues have been transplanted with the aim of generating an operational human immune system. Depending on the source of human cells and the extend of the transplantation of human tissues, these mice possess varying degrees of the human immune system in a shell of mouse nonimmune cells. A large range of cytokines mediates communication between immune cells and between immune cells and nonimmune cells of various organs. While human cells will produce some of these cytokines, mouse cells will produce others. Thus the humanized mouse will contain a mix of human and mouse cytokines and in the absence of perfect species cross-reactivity, these cytokines will affect mouse and human cells differentially. In addition, for heterodimeric cytokines there is a possibility that species-hybrid of these cytokines are produced, where one chain of the dimer is of human origin while the other is from mouse origin, giving rise to new molecules with different properties. Here we explore the impact of species specificity of cytokines in the context of humanized mice; and use a predictive model of species specificity based on amino acid identity between cytokines from different species to explore which cytokines will most likely be affected.