Developing biological interventions to control human immunodeficiency virus (HIV) replication in the absence of antiretroviral therapy (ART) could contribute to the development of a functional cure. ...As a potential alternative to ART, the interleukin-15 (IL-15) superagonist ALT-803 has been shown to boost the number and function of HIV-specific CD8
T and NK cell populations
Four simian immunodeficiency virus (SIV)-positive rhesus macaques, three of whom possessed major histocompatibility complex alleles associated with control of SIV and all of whom had received SIV vaccine vectors that had the potential to elicit CD8
T cell responses, were given ALT-803 in three treatment cycles. The first and second cycles of treatment were separated by 2 weeks, while the third cycle was administered after a 29-week break. ALT-803 transiently elevated the total CD8
effector and central memory T cell and NK cell populations in peripheral blood, while viral loads transiently decreased by ∼2 logs in all animals. Virus suppression was not sustained as T cells became less responsive to ALT-803 and waned in numbers. No effect on viral loads was observed in the second cycle of ALT-803, concurrent with downregulation of the IL-2/15 common γC and β chain receptors on both CD8
T cells and NK cells. Furthermore, populations of immunosuppressive T cells increased during the second cycle of ALT-803 treatment. During the third treatment cycle, responsiveness to ALT-803 was restored. CD8
T cells and NK cells increased again 3- to 5-fold, and viral loads transiently decreased again by 1 to 2 logs.
Overall, our data show that ALT-803 has the potential to be used as an immunomodulatory agent to elicit effective immune control of HIV/SIV replication. We identify mechanisms to explain why virus control is transient, so that this model can be used to define a clinically appropriate treatment regimen.
Contient : Navier, Claude-Louis-Henri-Marie ; Du Nazier, J., de la monnaie de Paris ; Niguet, C ; Noire de Sellier ; Nougarède de Fayet, Auguste ; O'Connell, J ; Ortolan, Joseph-Louis-Elzéar ; Otter, ...Francis ; Papot, A ; Pardeilhan-Mezin de, secrétaire général délégué de la préfecture de Haute-Garonne ; Paris. Mairie du IIe arrondissement ; Paris. Mairie du IIIe arrondissement ; Paris. Mairie du XIIe arrondissement ; Paris. Théâtre du Palais National (1850) ; Pascal, Em ; Pellissier Pierre-Augustin ?, agrégé de philosophie, 1849 ; Penard, Justin, docteur ; Penot ; Perron, comte Charles de ; Perry, sir Erskine ; Petit, Alexis ; Peyré, J.-Marie-Marcellin, professeur de physique à l'École normale de Versailles ; Peyronnet ; Phiquepal d'Arusmont, L.N., Mme ; Pierron, N ; Pinel-Grandchamp, Félix ; Pinheiro-Ferreira, Silvestre ; Poinsot, Louis ; Ploix, Charles-Martin ; Polonceau, A ; Pourtalès-Georgier, comte Henri de ; Préau, C ; Pingarben ; Profumo, Benedetto ; Poisson, Ch ; Pommier, E., directeur de collège à Lagny, Seine-et-Marne ; Prieur-Duperray, Gabriel ; Prieur-Duperray, Mary, Mme Gabriel
Numérisation effectuée à partir d'un document de substitution : R 130175.
Contains: Navier, Claude-Louis-Henri-Marie; Du Nazier, J., the currency of Paris; Niguet, C; Noire de Sellier; Nougaredes de Fayet, Auguste; O' Connell, J; Ortolan, Joseph-Louis-Elzéar; Otter, Francis; Papot, A; Pardeilhan-Mezin de, Secretary General Delegate of the Prefecture of Haute-Garonne; Paris. The second district town hall; Paris. The Third District Town Hall; Paris. Town Hall of the 13th arrondissement; Paris. National Palace Theatre (1850); Pascal, Em; Pellissier Pierre-Augustin?, Philosophy Aggregate, 1849; Penard, Justin, Doctor; Penot; Perron, Count Charles de; Perry, sir Erskine; Petit, Alexis; Peyré, J.-Marie-Marcellin, Professor of Physics at the Normal School of Versailles; Peyronnet; Phiquepal dArusmont, L.N., Mrs; Pierron, N; Pinel-Grandchamp, Felix; Pinheiro-Ferreira, Silvestre; Poinsot, Louis; Ploix, Charles-Martin; Polonceau, A; Most Georgier, Count Henri de; Préau, C; Pingarben; Profumo, Benedetto; Poisson, Ch;
Contient : Navier, Claude-Louis-Henri-Marie ; Du Nazier, J., de la monnaie de Paris ; Niguet, C ; Noire de Sellier ; Nougarède de Fayet, Auguste ; O'Connell, J ; Ortolan, Joseph-Louis-Elzéar ; Otter, Francis ; Papot, A ; Pardeilhan-Mezin de, secrétaire général délégué de la préfecture de Haute-Garonne ; Paris. Mairie du IIe arrondissement ; Paris. Mairie du IIIe arrondissement ; Paris. Mairie du XIIe arrondissement ; Paris. Théâtre du Palais National (1850) ; Pascal, Em ; Pellissier Pierre-Augustin ?, agrégé de philosophie, 1849 ; Penard, Justin, docteur ; Penot ; Perron, comte Charles de ; Perry, sir Erskine ; Petit, Alexis ; Peyré, J.-Marie-Marcellin, professeur de physique à l'École normale de Versailles ; Peyronnet ; Phiquepal d'Arusmont, L.N., Mme ; Pierron, N ; Pinel-Grandchamp, Félix ; Pinheiro-Ferreira, Silvestre ; Poinsot, Louis ; Ploix, Charles-Martin ; Polonceau, A ; Pourtalès-Georgier, comte Henri de ; Préau, C ; Pingarben ; Profumo, Benedetto ; Poisson, Ch ; Pommier, E., directeur de collège à Lagny, Seine-et-Marne ; Prieur-Duperray, Gabriel ; Prieur-Duperray, Mary, Mme Gabriel
Numérisation effectuée à partir d'un document de substitution : R 130175.
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