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.
| Original language | English |
|---|---|
| Article number | 13864 |
| Journal | Scientific Reports |
| Volume | 5 |
| DOIs | |
| Publication status | Published - Sep 7 2015 |
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Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice. / Fiume, Giuseppe; Scialdone, Annarita; Albano, Francesco; Rossi, Annalisa; Tuccillo, Franca Maria; Rea, Domenica; Palmieri, Camillo; Caiazzo, Elisabetta; Cicala, Carla; Bellevicine, Claudio; Falcone, Cristina; Vecchio, Eleonora; Pisano, Antonio; Ceglia, Simona; Mimmi, Selena; Iaccino, Enrico; Laurentiis, Annamaria De; Pontoriero, Marilena; Agosti, Valter; Troncone, Giancarlo; Mignogna, Chiara; Palma, Giuseppe; Arra, Claudio; Mallardo, Massimo; Maria Buonaguro, Franco; Scala, Giuseppe; Quinto, Ileana.
In: Scientific Reports, Vol. 5, 13864, 07.09.2015.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice
AU - Fiume, Giuseppe
AU - Scialdone, Annarita
AU - Albano, Francesco
AU - Rossi, Annalisa
AU - Tuccillo, Franca Maria
AU - Rea, Domenica
AU - Palmieri, Camillo
AU - Caiazzo, Elisabetta
AU - Cicala, Carla
AU - Bellevicine, Claudio
AU - Falcone, Cristina
AU - Vecchio, Eleonora
AU - Pisano, Antonio
AU - Ceglia, Simona
AU - Mimmi, Selena
AU - Iaccino, Enrico
AU - Laurentiis, Annamaria De
AU - Pontoriero, Marilena
AU - Agosti, Valter
AU - Troncone, Giancarlo
AU - Mignogna, Chiara
AU - Palma, Giuseppe
AU - Arra, Claudio
AU - Mallardo, Massimo
AU - Maria Buonaguro, Franco
AU - Scala, Giuseppe
AU - Quinto, Ileana
PY - 2015/9/7
Y1 - 2015/9/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84979872873&partnerID=8YFLogxK
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U2 - 10.1038/srep13864
DO - 10.1038/srep13864
M3 - Article
AN - SCOPUS:84979872873
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 13864
ER -