1. Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice.
- Author
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Fiume G, Scialdone A, Albano F, Rossi A, Tuccillo FM, Rea D, Palmieri C, Caiazzo E, Cicala C, Bellevicine C, Falcone C, Vecchio E, Pisano A, Ceglia S, Mimmi S, Iaccino E, de Laurentiis A, Pontoriero M, Agosti V, Troncone G, Mignogna C, Palma G, Arra C, Mallardo M, Buonaguro FM, Scala G, and Quinto I
- Subjects
- Animals, Cluster Analysis, Cytokines blood, Cytokines genetics, Cytokines metabolism, Gene Expression, Gene Expression Profiling, HIV Infections metabolism, HIV Infections virology, Lipopolysaccharides immunology, Lymphocyte Count, Lymphocyte Depletion, Lymphopoiesis, Mice, Mice, Transgenic, MicroRNAs genetics, NF-kappa B metabolism, T-Lymphocyte Subsets metabolism, Thymocytes cytology, Thymocytes immunology, Thymus Gland cytology, Thymus Gland immunology, Thymus Gland metabolism, Cell Differentiation, HIV Infections immunology, HIV-1 genetics, HIV-1 immunology, T-Lymphocyte Subsets cytology, T-Lymphocyte Subsets immunology, tat Gene Products, Human Immunodeficiency Virus genetics
- Abstract
Immune activation and chronic inflammation are hallmark features of HIV infection causing T-cell depletion and cellular immune dysfunction in AIDS. Here, we addressed the issue whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4(+) and CD8(+) T cells depletion in peripheral blood. In Tat-positive thymus, we observed the increased p65/NF-κB activity and deregulated expression of cytokines/chemokines and microRNA-181a-1, which are involved in T-lymphopoiesis. Upon LPS intraperitoneal injection, Tat-Tg mice developed an abnormal acute inflammatory response, which was characterized by enhanced lethality and production of inflammatory cytokines. Based on these findings, Tat-Tg mouse could represent an animal model for testing adjunctive therapies of HIV-1-associated inflammation and immune deregulation.
- Published
- 2015
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