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RESEARCH PRODUCT

Maintenance and Function of Human CD8+ T Cells and NK Cells in Humanized Mice

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description

Human CD8+ T lymphocytes and NK cells can be successfully engrafted in highly immuno-deficient mouse strains such as NOD/shi-SCID/γgcnull (NOG), NOD/SCID/IL2Rγnull (NSG), NOD/Rag1KO/γcnull (NRG), and BALB/c-Rag2KO/γcnull (BRG) mice following reconstitution with human CD34+ hematopoietic stem cells (HSCs) or, alternatively, upon adoptive transfer of peripheral blood mononuclear cells (PBMC). These humanized immune system (HIS) mice have evolved as a promising tool to study human CD8+ T cell and NK cell-mediated immune responses to cancer and infectious diseases and to explore new approaches in adoptive immunotherapy and vaccination. However, long-term generation of CD8+ T lymphocytes and NK cells is limited in the absence of human leukocyte antigen (HLA) class I expression, appropriate chemokines and trafficking signals to support proper homing into lymphoid tissues and reasonable concentrations of human cytokines to promote CD8+ T and NK cell development, maintenance and function. In this chapter we review the current status and the existing limitations of CD8+ T cell and NK cell biology in HIS mice and outline recent progress made using new substrains expressing human HLA molecules and exogenous supplementation of human cytokines to improve humanization.