tetano
Editor, Senior Moderator
J Virol. 2013 Sep 18. [Epub ahead of print]
PC61 (anti-CD25) treatment inhibits influenza-A expanded Tregs and severe lung pathology during a subsequent heterologous LCMV infection.
Kraft AR, Wlodarczyk MF, Kenney LL, Selin LK.
Source
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
Abstract
Prior immunity to influenza A (IAV) in mice changes the outcome to a subsequent LCMV infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8+ T-cells crossreactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4+ Foxp3+ Treg cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses might also contribute to enhancing lung pathology upon LCMV infection of IAV-immune mice. Tregs and IL-10 levels remained elevated in the lungs and mLNs throughout the acute LCMV response of IAV-immune mice. PC61-treatment used to decrease Treg did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection only in IAV-immune but not in na?ve mice. Associated with this decrease in pathology was a retention of Treg in the mLN and an unexpected partial clonal exhaustion of LCMV-specific CD8+ T-cell responses only in IAV-immune mice. PC61-treatment did not affect crossreactive memory CD8+ T-cell proliferation. These results suggest that in the absence of IAV-expanded Tregs, and in the presence of crossreactive memory, the LCMV-specific response was over-stimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Tregs generated during past infections can influence the characteristics of effector T-cell responses and immunopathology during subsequent heterologous infections. Thus, in humans with complex infection histories PC61-treatment may lead to unexpected results.
PMID:
24049180
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24049180
PC61 (anti-CD25) treatment inhibits influenza-A expanded Tregs and severe lung pathology during a subsequent heterologous LCMV infection.
Kraft AR, Wlodarczyk MF, Kenney LL, Selin LK.
Source
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
Abstract
Prior immunity to influenza A (IAV) in mice changes the outcome to a subsequent LCMV infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8+ T-cells crossreactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4+ Foxp3+ Treg cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses might also contribute to enhancing lung pathology upon LCMV infection of IAV-immune mice. Tregs and IL-10 levels remained elevated in the lungs and mLNs throughout the acute LCMV response of IAV-immune mice. PC61-treatment used to decrease Treg did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection only in IAV-immune but not in na?ve mice. Associated with this decrease in pathology was a retention of Treg in the mLN and an unexpected partial clonal exhaustion of LCMV-specific CD8+ T-cell responses only in IAV-immune mice. PC61-treatment did not affect crossreactive memory CD8+ T-cell proliferation. These results suggest that in the absence of IAV-expanded Tregs, and in the presence of crossreactive memory, the LCMV-specific response was over-stimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Tregs generated during past infections can influence the characteristics of effector T-cell responses and immunopathology during subsequent heterologous infections. Thus, in humans with complex infection histories PC61-treatment may lead to unexpected results.
PMID:
24049180
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24049180