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Viral antigen induces differentiation of Foxp3+ natural regulatory T cells in influenza virus-infected mice.


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.

SUBMITTER: Bedoya F 

PROVIDER: S-EPMC3703618 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Viral antigen induces differentiation of Foxp3+ natural regulatory T cells in influenza virus-infected mice.

Bedoya Felipe F   Cheng Guang-Shing GS   Leibow Abigail A   Zakhary Nardine N   Weissler Katherine K   Garcia Victoria V   Aitken Malinda M   Kropf Elizabeth E   Garlick David S DS   Wherry E John EJ   Erikson Jan J   Caton Andrew J AJ  

Journal of immunology (Baltimore, Md. : 1950) 20130510 12


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 und  ...[more]

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