Abstract:The Humanized hematopoietic stem cells (Hu-HSCs) model is a key model for simulating the differentiation and function of human T cells. However, due to the background of severe immune deficiency in reconstructed mice, thymic development is hindered or there is no thymic gland, lacking the site for T cell differentiation and maturation. It leads to insufficient reconstruction of human functional T cells in mice. Although the transplantation of human fetal thymus tissue can support the effective development of T cells in humanized mice, the scarcity of donor tissues and ethical issues have limited its wide application. Therefore, it is urgent to develop new types of thymus tissue to overcome the above limitations. This article systematically summarizes the basic characteristics of the Hu-HSCs mouse model and the human T-cell immune response ability induced by traditional fetal thymus transplantation. This paper mainly reviews the role of the novel thymus transplantation in promoting T cell development and regulating the immune response mediated by human T cells, reveals its potential mechanism and significance in enhancing human immunity, and is expected to provide theoretical basis and technical support for the development of new humanized mouse models.