GSBS Student Publications

Student Author(s)

Laurie L. Kenney

GSBS Program

Immunology & Microbiology

UMMS Affiliation

Department of Pathology

Date

12-1-2013

Document Type

Article

Disciplines

Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy | Virology

Abstract

Prior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (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 cross-reactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4(+) Foxp3(+) T-regulatory (Treg) cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses also contributes to enhancing lung pathology upon LCMV infection of IAV-immune mice. Treg cell and interleukin-10 (IL-10) levels remained elevated in the lungs and mediastinal lymph nodes (mLNs) throughout the acute LCMV response of IAV-immune mice. PC61 treatment, used to decrease Treg cell levels, did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection in IAV-immune but not in naive 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 cross-reactive memory CD8(+) T-cell proliferation. These results suggest that in the absence of IAV-expanded Treg cells and in the presence of cross-reactive memory, the LCMV-specific response was overstimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Treg cells 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.

Rights and Permissions

Copyright © 2013, American Society for Microbiology. Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

DOI of Published Version

10.1128/JVI.00936-13

Source

J Virol. 2013 Dec;87(23):12636-47. doi: 10.1128/JVI.00936-13. Epub 2013 Sep 18. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Journal of virology

PubMed ID

24049180

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.