T Cell Development and Responses in Human Immune System Mice

Annu Rev Immunol. 2025 Apr;43(1):83-112. doi: 10.1146/annurev-immunol-082223-041615. Epub 2024 Dec 20.

Abstract

Human Immune System (HIS) mice constructed with mature human immune cells or with human hematopoietic stem cells and thymic tissue have provided an important tool for human immunological research. In this article, we first review the different types of HIS mice based on human tissues transplanted and sources of the tissues. We then focus on knowledge of human T cell development and responses obtained using HIS mouse models. These areas include the development of human T cell subsets, with a focus on αβ conventional T cells and regulatory T cells, and human T cell responses in the settings of infection, transplantation rejection and tolerance, autoimmune disease, cancer immunotherapy, and regulatory T cell therapy. We also discuss the limitations and potential future applications of HIS mouse models.

Keywords: Human Immune System mice; T cell development; T cell responses; homeostasis; regulatory T cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Disease Models, Animal
  • Humans
  • Immune System* / cytology
  • Mice
  • T-Lymphocyte Subsets* / immunology
  • T-Lymphocyte Subsets* / metabolism
  • T-Lymphocytes* / immunology