Effector CD8+ T cell recovered from an influenza pneumonia to differentiate to a state of focused gene expression

Dana R. Marshall, Elvia Olivas, Samita Andreansky, Nicole L. La Gruta, Geoff A. Neale, Astrid Gutierrez, David G. Wichlan, Suzette Wingo, Cheng Cheng, Peter C. Doherty, Stephen J. Turner

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The restriction of influenza A virus replication to mouse respiratory epithelium means that this host response is anatomically compartmentalized, on the one hand, to sites of T cell stimulation and proliferation in the secondary lymphoid tissue and, on the other hand, to the site of effector T cell function and pathology in the pneumonic lung. Thus, it is hardly surprising that virus-specific CD8+ T cells recovered by bronchoalveolar lavage (BAL) from the infected respiratory tract seem more "activated" in terms of both cytolytic activity and cytokine production than those cells isolated from the spleen. The present analysis uses Affymetrix microarray technology to compare profiles of gene expression in these two lineage-related, yet anatomically separate, lymphocyte populations. Ninety differentially expressed genes were identified for influenza-specific CD8+DbNP 366+ T cells obtained directly ex vivo by BAL or spleen disruption, with nine genes being further analyzed by quantitative, real-time PCR at the population level, Integrin αE, for example, was shown by Affymetrix and real-time mRNA analyses and then by single-cell PCR and protein staining to be present at a much higher prevalence on the BAL CD8 +DbNP366+ set. The unpredicted finding, however, was that mRNA expression for 75% of the 90 genes was lower in T cells from the BAL than from the spleen. Apparently, the localization of virus-specific CD8+ T cells to the site of virus-induced pathology is associated with a narrowing, or "focusing," of gene expression that favors enhanced effector function in the damaged, "high-antigen load" environment of the pneumonic lung.

Original languageEnglish (US)
Pages (from-to)6074-6079
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number17
DOIs
StatePublished - Apr 26 2005

Keywords

  • Affymetrix gene array
  • Cytotoxic T cell
  • Influenza A virus
  • Viral immunology

ASJC Scopus subject areas

  • Genetics
  • General

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    Marshall, D. R., Olivas, E., Andreansky, S., La Gruta, N. L., Neale, G. A., Gutierrez, A., Wichlan, D. G., Wingo, S., Cheng, C., Doherty, P. C., & Turner, S. J. (2005). Effector CD8+ T cell recovered from an influenza pneumonia to differentiate to a state of focused gene expression. Proceedings of the National Academy of Sciences of the United States of America, 102(17), 6074-6079. https://doi.org/10.1073/pnas.0501960102