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

✍ Scribed by Hayley A. Croom; Alice E. Denton; Sophie A. Valkenburg; Natasha G. Swan; Matthew R. Olson; Stephen J. Turner; Peter C. Doherty; Katherine Kedzierska

• Book ID: 102824912
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 727 KB
• Volume: 41
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.201040625

✦ Synopsis

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 (4d500) for two immunodominant CD8 1 responses during the course of a localized low-load influenza infection in mice. CD8 1 T cells stained with the D b NP 366 and D b PA 224 tetramers were characterized as IL-7Ra hi , IL-7Ra hi CD62L hi or IL-7Ra hi KLRG1 lo . While the D b NP 366 -and D b PA 224 -specific responses were comparable in size, decay kinetics and memory precursor frequency, their expansion characteristics differed. This correlated with a divergence in the IL-7Ra hi , IL-7Ra hi CD62L hi and IL-7Ra hi KLRG1 lo phenotypes on effector, but not naı ¨ve, CD8 1 populations. That effect was abrogated by priming with viruses engineered to present equivalent levels of NP 366 and PA 224 peptides, indicating that memory phenotypes reflect early antigenic experience rather than memory potential. Thus, the IL-7Ra hi KLRG1 lo 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-7Ra hi KLRG1 lo CD8 1 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.