Memory precursor phenotype of CD8+ T cells reflects early antigenic experience rather than memory numbers in a model of localized acute influenza infection

Abstract

The mechanistic basis of memory T-cell development is poorly defined. Phenotypic markers that define precursors at effector stages have been characterized for acute systemic infections with high antigen load. We asked whether such markers can identify memory precursors from early effectors (d6) to late memory (>d500) for two immunodominant CD8+ responses during the course of a localized low-load influenza infection in mice. CD8+ T cells stained with the DbNP366 and DbPA224 tetramers were characterized as IL-7Rαhi, IL-7RαhiCD62Lhi or IL-7RαhiKLRG1lo. While the DbNP366- and DbPA224-specific responses were comparable in size, decay kinetics and memory precursor frequency, their expansion characteristics differed. This correlated with a divergence in the IL-7Rαhi, IL-7RαhiCD62Lhi and IL-7RαhiKLRG1lo phenotypes on effector, but not naïve, CD8+ populations. That effect was abrogated by priming with viruses engineered to present equivalent levels of NP366 and PA224 peptides, indicating that memory phenotypes reflect early antigenic experience rather than memory potential. Thus, the IL-7RαhiKLRG1lo phenotype had a poor predictive value in identifying memory precursors in the spleen and at the site of infection. Greater consistency in influenza-specific IL-7RαhiKLRG1loCD8+ T-cell numbers was found in draining lymph nodes, suggesting that this may be the preferential site for memory establishment and maintenance following localized virus infections. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.