Interleukin-2-Mediated Engraftment of Human Peripheral Blood Mononuclear Cells in Immunodeficient Mice to Develop a Model of HIV Infection: New Criteria for Engraftment Monitoring.

Graft failure and graft-versus-host disease are the main limiting factors for the engraftment of not only xenogeneic but also allogeneic grafts. Long-term engraftment of human immune cells in mice with severe combined immunodeficiency and IL2rg deletion is key to the success of long-term studies in modeling human immunodeficiency virus (HIV) infection. Human peripheral blood mononuclear cells were injected intravenously into males of one strain and females of two other strains of immunodeficient mice. Before the injection of human cells, mice of each strain were irradiated with three different doses. Interleukin-2 was administered to 50% of mice within 5 days of human cell injection. Its effect was assessed by monitoring graft-versus-host disease, survival, complete blood count (CBC) indices, quantification of human cells in whole blood, pathological changes, and immunohistochemical detection of human cells in tissues. Furthermore, the applicability of correlating immune-inflammation indices with mouse body weight (BW) dynamics, graft-versus-host disease (GVHD) progression, degrees of chimerism and human T-helper cells was determined for the first time. As a result of this work, a panel of biomarkers was developed for predicting the long-term welfare of mice with elements of the human immune system (HIS) in long-term studies, including HIV testing.