Vaccination in humans generates broad T cell cytokine responses

Stephen C. De Rosa, Fabien X. Lu, Joanne Yu, Stephen P. Perfetto, Judith Falloon, Susan Moser, Thomas G. Evans, Richard Koup, Chris J Miller, Mario Roederer

Research output: Contribution to journalArticle

164 Scopus citations

Abstract

In recent years, the quantification of T cell responses to pathogens or immunogens has become a common tool in the evaluation of disease pathogenesis or vaccine immunogenicity. Such measurements are usually limited to enumerating IFN-γ-producing cells after ex vivo stimulation with Ag, but little is known about the phenotype or complete functional repertoire of the Ag-specific cells. We used 12-color flow cytometry to characterize Ag-speciflc T cells elicited by vaccines or natural infection to determine lineage and differentiation status as well as the capacity to produce four cytekiaes (IFN-γ, TNF-α, IL-2; and IL-4) and a chemokine (MIP1β). As expected, responding cells had a typical memory phenotype; however, the cytokine profiles associated with the responses were highly complex. The pattern of cytokine coexpression in response to specific Ags was a skewed subset of the complete repertoire (revealed by polyclonal stimulation). We found significant differences in the patterns of cytokines elicited by vaccination (where IFN-γ was by far a subdominant response) vs natural infection; in addition, there was fairly significant fate-subject variation. Our findings illustrate the limitation of the evaluation of immune responses using single functional measurements (such as IFN-γ); in fact, it is likely that sensitive evaluation of Ag-specific T cells will require the coordinate measurement of several cytokines. The presence and variability of ihese complex response profiles introduce the possibility that selective functional expression patterns may provide correlates for vaccine efficacy or disease progression.

Original languageEnglish (US)
Pages (from-to)5372-5380
Number of pages9
JournalJournal of Immunology
Volume173
Issue number9
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Immunology

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    De Rosa, S. C., Lu, F. X., Yu, J., Perfetto, S. P., Falloon, J., Moser, S., Evans, T. G., Koup, R., Miller, C. J., & Roederer, M. (2004). Vaccination in humans generates broad T cell cytokine responses. Journal of Immunology, 173(9), 5372-5380.