Increase in IFN gamma-IL-2(+) Cells in Recent Human CD4 T Cell Responses to 2009 Pandemic H1N1 Influenza

• Type of Material: Article
• Authors: Jason M. Weaver, University of Rochester; Hongmei Yang, University of Rochester; David Roumanes, University of Rochester; Frances Eun-Hyung Lee, Emory University; Hulin Wu, University of Rochester; John J. Treanor, University of Rochester; Tim R. Mosmann, University of Rochester
• Language: English
• Date: 2013-03-20
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Weaver et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0057275
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 3
• Start Page: e57275
• End Page: e57275
• Grant/Funding Information: This work was supported by contract HHSN266200700008C to JJT, and by grants K23 AI67501 and HHSN266200500030C (N01-AI50029) to FEL and AI054953 to TRM from the National Institutes of Health.
• Keywords: CENTRAL MEMORY; IN-VIVO; CXC CHEMOKINE RECEPTOR-5; A VIRUS; EFFECTOR FUNCTIONS; VACCINATION; Science & Technology - Other Topics; SUBSETS; VACCINES; Multidisciplinary Sciences; IMMUNE-RESPONSES; GAMMA-SECRETING CELLS; Science & Technology
• Research Categories: Health Sciences, Immunology

Abstract

Human CD4 T cell recall responses to influenza virus are strongly biased towards Type 1 cytokines, producing IFNγ, IL-2 and TNFα. We have now examined the effector phenotypes of CD4 T cells in more detail, particularly focusing on differences between recent versus long-term, multiply-boosted responses. Peptides spanning the proteome of temporally distinct influenza viruses were distributed into pools enriched for cross-reactivity to different influenza strains, and used to stimulate antigen-specific CD4 T cells representing recent or long-term memory. In the general population, peptides unique to the long-circulating influenza A/New Caledonia/20/99 (H1N1) induced Th1-like responses biased toward the expression of IFNγ+TNFα+ CD4 T cells. In contrast, peptide pools enriched for non-cross-reactive peptides of the pandemic influenza A/California/04/09 (H1N1) induced more IFNγ-IL-2+TNFα+ T cells, similar to the IFNγ-IL-2+ non-polarized, primed precursor T cells (Thpp) that are a predominant response to protein vaccination. These results were confirmed in a second study that compared samples taken before the 2009 pandemic to samples taken one month after PCR-confirmed A/California/04/09 infection. There were striking increases in influenza-specific TNFα+, IFNγ+, and IL-2+ cells in the post-infection samples. Importantly, peptides enriched for non-cross-reactive A/California/04/09 specificities induced a higher proportion of Thpp-like IFNγ-IL-2+TNFα+ CD4 T cells than peptide pools cross-reactive with previous influenza strains, which induced more Th1 (IFNγ+TNFα+) responses. These IFNγ-IL-2+TNFα+ CD4 T cells may be an important target population for vaccination regimens, as these cells are induced upon infection, may have high proliferative potential, and may play a role in providing future effector cells during subsequent infections.