2006
DOI: 10.1084/jem.20061462
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Resolution of a chronic viral infection after interleukin-10 receptor blockade

Abstract: A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function of T cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulte… Show more

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Cited by 508 publications
(623 citation statements)
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References 65 publications
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“…Interestingly, IL-10 blockade, similar to results reported by Alatrakchi et al (58), enhanced HCV-specific IFNγ response to HCV Core peptides in CD4-depleted as well as CD8-depleted PBMC, suggesting that IL-10 production by CD4 − and/or CD8 − cells (including non-T-cells such as monocytes, B-cells or NK cells) participate in HCVspecific immune regulation. Enhancement of HCV-specific effector T-cell response by IL-10R blockade has interesting therapeutic implications, particularly in light of virus control with restoration of effector T-cell function in murine LCMV infection demonstrated by IL-10 blockade in-vivo (59,60). However, the inverse association between HCV-specific Tr1 response and cirrhosis in our study suggests further caution in applying IL-10 blockade to HCV infection.…”
Section: Discussionmentioning
confidence: 65%
“…Interestingly, IL-10 blockade, similar to results reported by Alatrakchi et al (58), enhanced HCV-specific IFNγ response to HCV Core peptides in CD4-depleted as well as CD8-depleted PBMC, suggesting that IL-10 production by CD4 − and/or CD8 − cells (including non-T-cells such as monocytes, B-cells or NK cells) participate in HCVspecific immune regulation. Enhancement of HCV-specific effector T-cell response by IL-10R blockade has interesting therapeutic implications, particularly in light of virus control with restoration of effector T-cell function in murine LCMV infection demonstrated by IL-10 blockade in-vivo (59,60). However, the inverse association between HCV-specific Tr1 response and cirrhosis in our study suggests further caution in applying IL-10 blockade to HCV infection.…”
Section: Discussionmentioning
confidence: 65%
“…The existence of viruses with IL-10 homologs reveals an evolutionary advantage to enhanced IL-10 levels for an invading virus (Griffiths 2002, SalekArdakani et al 2002. Studies with peripheral blood leukocytes found that early after infection with dengue virus (DENV), a flavivirus, increased IL-10 production induces lasting T cell inactivation and decreases the control of virus infection (Ejrnaes et al 2006). Consequently, the interaction of immunosuppressive IL-10-producing cells with T cells early during arbovirus infection may result in the loss of T-cell responsiveness, facilitate an enhancement of viral replication, and a impaired adaptive immune response.…”
Section: Immunomodulation In the Context Of Arbovirus Infectionmentioning
confidence: 99%
“…Besides a role for immunoregulatory cytokines such as 15], , a role for inhibitory receptor expression (reviewed in [18]) and perhaps regulatory T cells [19] C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol.…”
Section: Introductionmentioning
confidence: 99%
“…This T-cell dysfunction, also termed CD8 + T-cell exhaustion, is well studied after infection of mice with a high dose of LCMV clone 13 or LCMV-Docile [13]. Infection of mice with a low dose of the same virus strains results in an acute resolved infection [13].Besides a role for immunoregulatory cytokines such as 15], , a role for inhibitory receptor expression (reviewed in [18]) and perhaps regulatory T cells [19] C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol.…”
mentioning
confidence: 99%