Increased memory conversion of naïve CD8 t cells activated during late phases of acute virus infection due to decreased cumulative antigen exposure

Georgia Fousteri, Amy Dave, Amy Juedes, Therese Juntti, Bret Morin, Lisa Togher, Donna L. Farber, Matthias von Herrath

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Memory CD8 T cells form an essential part of protective immunity against viral infections. Antigenic load, costimulation, CD4-help, cytokines and chemokines fluctuate during the course of an antiviral immune response thus affecting CD8 T cell activation and memory conversion. Methodology/Principal Findings: In the present study, nai{dotless}̈ve TCR transgenic LCMV-specific P14 CD8 T cells engaged at a late stage during the acute antiviral LCMV response showed reduced expansion kinetics but greater memory conversion in the spleen. Such late activated cells displayed a memory precursor effector phenotype already at the peak of the systemic antiviral response, suggesting that the environment determined their fate during antigen encounter. In the spleen, the majority of late transferred cells exhibited a central memory phenotype compared to the effector memory displayed by the early transferred cells. Increasing the inflammatory response by exogenous administration of IFNγ, PolyI:C or CpG did not affect memory conversion in the late transferred group, suggesting that the diverging antigen load early versus later during acute infection had determined their fate. In agreement, reduction in the LCMV antigenic load after ribavirin treatment enhanced the contribution of early transferred cells to the long lasting memory pool. Conclusions/Significance: Our results show that nai{dotless}̈ve CD8 cells, exposed to reduced duration or concentration of antigen during viral infection convert into memory more efficiently, an observation that could have significant implications for vaccine design.

Original languageEnglish
Article numbere14502
JournalPLoS One
Volume6
Issue number1
DOIs
Publication statusPublished - 2011

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Virus Diseases
Viruses
antigens
Antigens
Data storage equipment
viruses
Lymphocytic choriomeningitis virus
infection
T-cells
Antiviral Agents
cells
T-Lymphocytes
T-lymphocytes
Spleen
Phenotype
spleen
Ribavirin
phenotype
Chemokines
viral antigens

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Increased memory conversion of naïve CD8 t cells activated during late phases of acute virus infection due to decreased cumulative antigen exposure. / Fousteri, Georgia; Dave, Amy; Juedes, Amy; Juntti, Therese; Morin, Bret; Togher, Lisa; Farber, Donna L.; von Herrath, Matthias.

In: PLoS One, Vol. 6, No. 1, e14502, 2011.

Research output: Contribution to journalArticle

Fousteri, Georgia ; Dave, Amy ; Juedes, Amy ; Juntti, Therese ; Morin, Bret ; Togher, Lisa ; Farber, Donna L. ; von Herrath, Matthias. / Increased memory conversion of naïve CD8 t cells activated during late phases of acute virus infection due to decreased cumulative antigen exposure. In: PLoS One. 2011 ; Vol. 6, No. 1.
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