Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice.
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.
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Giuseppe
G
Fiume
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Annarita
A
Scialdone
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Francesco
F
Albano
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Annalisa
A
Rossi
Molecular Biology and Viral Oncogenesis Unit, Department of Experimental Oncology, Istituto Nazionale Tumori "Fondazione Giovanni Pascale", IRCCS, 80131, Naples, Italy.
Franca Maria
FM
Tuccillo
Molecular Biology and Viral Oncogenesis Unit, Department of Experimental Oncology, Istituto Nazionale Tumori "Fondazione Giovanni Pascale", IRCCS, 80131, Naples, Italy.
Domenica
D
Rea
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Camillo
C
Palmieri
Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.
Elisabetta
E
Caiazzo
Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.
Carla
C
Cicala
Department of Public Health, University of Naples "Federico II", Via Sergio Pansini 5, 80131, Naples, Italy.
Claudio
C
Bellevicine
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Cristina
C
Falcone
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Eleonora
E
Vecchio
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Antonio
A
Pisano
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Simona
S
Ceglia
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Selena
S
Mimmi
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Enrico
E
Iaccino
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Annamaria
A
de Laurentiis
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Marilena
M
Pontoriero
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Valter
V
Agosti
Department of Public Health, University of Naples "Federico II", Via Sergio Pansini 5, 80131, Naples, Italy.
Giancarlo
G
Troncone
Science of Health Department, University of Catanzaro "Magna Graecia", Italy.
Chiara
C
Mignogna
Molecular Biology and Viral Oncogenesis Unit, Department of Experimental Oncology, Istituto Nazionale Tumori "Fondazione Giovanni Pascale", IRCCS, 80131, Naples, Italy.
Giuseppe
G
Palma
Molecular Biology and Viral Oncogenesis Unit, Department of Experimental Oncology, Istituto Nazionale Tumori "Fondazione Giovanni Pascale", IRCCS, 80131, Naples, Italy.
Claudio
C
Arra
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Sergio Pansini 5, 80131, Naples, Italy.
Massimo
M
Mallardo
Molecular Biology and Viral Oncogenesis Unit, Department of Experimental Oncology, Istituto Nazionale Tumori "Fondazione Giovanni Pascale", IRCCS, 80131, Naples, Italy.
Franco Maria
FM
Buonaguro
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Giuseppe
G
Scala
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa, 88100, Catanzaro, Italy.
Ileana
I
Quinto
D000818:Animals; D002454:Cell Differentiation; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D038041:Lymphopoiesis; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D016207:Cytokines; D008070:Lipopolysaccharides; D035683:MicroRNAs; D016328:NF-kappa B; D054322:tat Gene Products, Human Immunodeficiency Virus