tetano
Editor, Senior Moderator
FASEB J. 2014 Nov 20. pii: fj.14-260687. [Epub ahead of print]
The administration of oseltamivir results in reduced effector and memory CD8+ T cell responses to influenza and affects protective immunity.
Marois I1, Cloutier A1, Garneau E1, Lesur O2, Richter MV3.
Author information
Abstract
The clinical benefits of oseltamivir (Tamiflu) are well established, but the effects of antiviral treatment on the immune response are poorly understood. By use of flow cytometric analyses and the mouse model, we thoroughly investigated the impact of such a treatment on the immune response and the generation of protective immunity to influenza. We demonstrated that influenza-specific CD8+ effector T cell recruitment was reduced up to 81% in the lungs of mice treated with oseltamivir (5 or 50 mg/kg twice daily; EC50 49 nM in vitro) compared to saline controls, but cell generation was unaffected in draining lymph nodes. Importantly, we showed that oseltamivir administration significantly decreased the pools of tissue-resident and circulating effector memory (93.7%) and central memory CD8+ T cells (45%) compared to saline controls. During heterologous secondary infection, a decreased memory CD8+ T cell pool combined with reduced generation of secondary influenza-specific effectors in the lymph nodes resulted in 10-fold decreased CD8+ T cell recall responses, which increased mouse morbidity and delayed viral clearance. Furthermore, antiviral administration led to a significant 5.7-fold decreased production of functional anti-influenza antibodies. Thus, our study demonstrates that antiviral treatment affects the development of the adaptive immune response and protective immunity against influenza.-Marois, I., Cloutier, A., Garneau, ?., Lesur, O., Richter, M. V. The administration of oseltamivir results in reduced effector and memory CD8+ T cell responses to influenza and affects protective immunity.
? FASEB.
KEYWORDS:
Tamiflu; adaptive immune response; antiviral; flu; immunologic consequences
PMID:
25414485
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25414485
The administration of oseltamivir results in reduced effector and memory CD8+ T cell responses to influenza and affects protective immunity.
Marois I1, Cloutier A1, Garneau E1, Lesur O2, Richter MV3.
Author information
Abstract
The clinical benefits of oseltamivir (Tamiflu) are well established, but the effects of antiviral treatment on the immune response are poorly understood. By use of flow cytometric analyses and the mouse model, we thoroughly investigated the impact of such a treatment on the immune response and the generation of protective immunity to influenza. We demonstrated that influenza-specific CD8+ effector T cell recruitment was reduced up to 81% in the lungs of mice treated with oseltamivir (5 or 50 mg/kg twice daily; EC50 49 nM in vitro) compared to saline controls, but cell generation was unaffected in draining lymph nodes. Importantly, we showed that oseltamivir administration significantly decreased the pools of tissue-resident and circulating effector memory (93.7%) and central memory CD8+ T cells (45%) compared to saline controls. During heterologous secondary infection, a decreased memory CD8+ T cell pool combined with reduced generation of secondary influenza-specific effectors in the lymph nodes resulted in 10-fold decreased CD8+ T cell recall responses, which increased mouse morbidity and delayed viral clearance. Furthermore, antiviral administration led to a significant 5.7-fold decreased production of functional anti-influenza antibodies. Thus, our study demonstrates that antiviral treatment affects the development of the adaptive immune response and protective immunity against influenza.-Marois, I., Cloutier, A., Garneau, ?., Lesur, O., Richter, M. V. The administration of oseltamivir results in reduced effector and memory CD8+ T cell responses to influenza and affects protective immunity.
? FASEB.
KEYWORDS:
Tamiflu; adaptive immune response; antiviral; flu; immunologic consequences
PMID:
25414485
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25414485