Continuous Effector CD8+ T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population

H. Hamlet Chu, Shiao Wei Chan, John Paul Gosling, Nicolas Blanchard, Alexandra Tsitsiklis, Grant Lythe, Nilabh Shastri, Carmen Molina-París, Ellen A. Robey

Research output: Contribution to journalArticle

Abstract

Highly functional CD8+ effector T (Teff) cells can persist in large numbers during controlled persistent infections, as exemplified by rare HIV-infected individuals who control the virus. Here we examined the cellular mechanisms that maintain ongoing T effector responses using a mouse model for persistent Toxoplasma gondii infection. In mice expressing the protective MHC-I molecule, H-2Ld, a dominant T effector response against a single parasite antigen was maintained without a contraction phase, correlating with ongoing presentation of the dominant antigen. Large numbers of short-lived Teff cells were continuously produced via a proliferative, antigen-dependent intermediate (Tint) population with a memory-effector hybrid phenotype. During an acute, resolved infection, decreasing antigen load correlated with a sharp drop in the Tint cell population and subsequent loss of the ongoing effector response. Vaccination approaches aimed at the development of Tint populations might prove effective against pathogens that lead to chronic infection.

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalImmunity
Volume45
Issue number1
DOIs
StatePublished - Jul 19 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Chu, H. H., Chan, S. W., Gosling, J. P., Blanchard, N., Tsitsiklis, A., Lythe, G., Shastri, N., Molina-París, C., & Robey, E. A. (2016). Continuous Effector CD8+ T Cell Production in a Controlled Persistent Infection Is Sustained by a Proliferative Intermediate Population. Immunity, 45(1), 159-171. https://doi.org/10.1016/j.immuni.2016.06.013