tetano
Editor, Senior Moderator
J Immunol. 2013 May 10. [Epub ahead of print]
Viral Antigen Induces Differentiation of Foxp3+ Natural Regulatory T Cells in Influenza Virus-Infected Mice.
Bedoya F, Cheng GS, Leibow A, Zakhary N, Weissler K, Garcia V, Aitken M, Kropf E, Garlick DS, Wherry EJ, Erikson J, Caton AJ.
Source
The Wistar Institute, Philadelphia, PA 19104.
Abstract
We examined the formation, participation, and functional specialization of virus-reactive Foxp3+ regulatory T cells (Tregs) in a mouse model of influenza virus infection. "Natural" Tregs generated intrathymically, based on interactions with a self-peptide, proliferated in response to a homologous viral Ag in the lungs and, to a lesser extent, in the lung-draining mediastinal lymph nodes (medLNs) of virus-infected mice. In contrast, conventional CD4+ T cells with identical TCR specificity underwent little or no conversion to become "adaptive" Tregs. The virus-reactive Tregs in the medLNs and the lungs of infected mice upregulated a variety of molecules associated with Treg activation, as well as acquired expression of molecules (T-bet, Blimp-1, and IL-10) that confer functional specialization to Tregs. Notably, however, the phenotypes of the T-bet+ Tregs obtained from these sites were distinct, because Tregs isolated from the lungs expressed significantly higher levels of T-bet, Blimp-1, and IL-10 than did Tregs from the medLNs. Adoptive transfer of Ag-reactive Tregs led to decreased proliferation of antiviral CD4+ and CD8+ effector T cells in the lungs of infected hosts, whereas depletion of Tregs had a reciprocal effect. These studies demonstrate that thymically generated Tregs can become activated by a pathogen-derived peptide and acquire discrete T-bet+ Treg phenotypes while participating in and modulating an antiviral immune response.
PMID:
23667113
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23667113
Viral Antigen Induces Differentiation of Foxp3+ Natural Regulatory T Cells in Influenza Virus-Infected Mice.
Bedoya F, Cheng GS, Leibow A, Zakhary N, Weissler K, Garcia V, Aitken M, Kropf E, Garlick DS, Wherry EJ, Erikson J, Caton AJ.
Source
The Wistar Institute, Philadelphia, PA 19104.
Abstract
We examined the formation, participation, and functional specialization of virus-reactive Foxp3+ regulatory T cells (Tregs) in a mouse model of influenza virus infection. "Natural" Tregs generated intrathymically, based on interactions with a self-peptide, proliferated in response to a homologous viral Ag in the lungs and, to a lesser extent, in the lung-draining mediastinal lymph nodes (medLNs) of virus-infected mice. In contrast, conventional CD4+ T cells with identical TCR specificity underwent little or no conversion to become "adaptive" Tregs. The virus-reactive Tregs in the medLNs and the lungs of infected mice upregulated a variety of molecules associated with Treg activation, as well as acquired expression of molecules (T-bet, Blimp-1, and IL-10) that confer functional specialization to Tregs. Notably, however, the phenotypes of the T-bet+ Tregs obtained from these sites were distinct, because Tregs isolated from the lungs expressed significantly higher levels of T-bet, Blimp-1, and IL-10 than did Tregs from the medLNs. Adoptive transfer of Ag-reactive Tregs led to decreased proliferation of antiviral CD4+ and CD8+ effector T cells in the lungs of infected hosts, whereas depletion of Tregs had a reciprocal effect. These studies demonstrate that thymically generated Tregs can become activated by a pathogen-derived peptide and acquire discrete T-bet+ Treg phenotypes while participating in and modulating an antiviral immune response.
PMID:
23667113
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23667113