Inhibition of Acute in vivo Human Immunodeficiency Virus Infection by Human Interleukin 10 Treatment of SCID Mice Implanted with Human Fetal Thymus and Liver

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 7; pp. 3126 - 3131
• Main Authors: Kollmann, Tobias R., Pettoello-Mantovani, Massimo, Katopodis, Nikos F., Hachamovitch, Moshe, Rubinstein, Arye, Kim, Ana, Goldstein, Harris
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 02.04.1996; National Acad Sciences; National Academy of Sciences
• Subjects: AIDS/HIV; Animals; Antigens, CD - analysis; Blood; Blood plasma; Brain; Cytokines; Cytokines - biosynthesis; Dosage; Fetal Tissue Transplantation - immunology; Flow Cytometry; Gene Expression; HIV; HIV infections; HIV Infections - immunology; HIV Infections - prevention & control; HIV Infections - therapy; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immunity (Disease); Infections; Interferon-gamma - biosynthesis; Interleukin-10 - therapeutic use; Liver; Liver Transplantation - immunology; Messenger RNA; Mice; Mice, SCID; Monocytes; Monocytes - immunology; Polymerase Chain Reaction; RNA, Viral - blood; Rodents; T lymphocytes; T-Lymphocytes - immunology; Thymus Gland - immunology; Thymus Gland - transplantation; Transplantation, Heterologous - immunology; Transplants & implants; Virus Replication
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.7.3126

To improve the usefulness of in vivo models for the investigation of the pathophysiology of human immunodeficiency virus (HIV) infection, we modified the construction of SCID mice implanted with human fetal thymus and liver (thy/liv-SCID-hu mice) so that the peripheral blood of the mice contained significant numbers of human monocytes and T cells. After inoculation with HIV-159, a primary patient isolate capable of infecting monocytes and T cells, the modified thy/liv-SCID-hu mice developed disseminated HIV infection that was associated with plasma viremia. The development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-159 was inhibited by acute treatment with human interleukin (IL) 10 but not with human IL-12. The human peripheral blood mononuclear cells in these modified thy/liv-SCID-hu mice were responsive in vivo to treatment with exogenous cytokines. Human interferon γ expression in the circulating human peripheral blood mononuclear cells was induced by treatment with IL-12 and inhibited by treatment with IL-10. Thus, these modified thy/liv-SCID-hu mice should prove to be a valuable in vivo model for examining the role of immunomodulatory therapy in modifying HIV infection. Furthermore, our demonstration of the in vivo inhibitory effect of IL-10 on acute HIV infection suggests that further studies may be warranted to evaluate whether there is a role for IL-10 therapy in preventing HIV infection in individuals soon after exposure to HIV such as for children born to HIV-infected mothers.