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Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice

2015; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/srep13864

2045-2322

Giuseppe Fiume, Annarita Scialdone, F. Albano, Annalisa Rossi, Franca Maria Tuccillo, Domenica Rea, Camillo Palmieri, Elisabetta Caiazzo, Carla Cicala, Claudio Bellevicine, Cristina Falcone, Eleonora Vecchio, Antonio Pisano, Simona Ceglia, Selena Mimmi, Enrico Iaccino, Annamaria de Laurentiis, Marilena Pontoriero, Valter Agosti, Giancarlo Troncone, Chiara Mignogna, Giuseppe Palma, Claudio Arra, Massimo Mallardo, Franco M. Buonaguro, Giuseppe Scala, Ileana Quinto,

T-cell and Retrovirus Studies

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.