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Immunity. 2016 Jul 19;45(1):159-71. doi: 10.1016/j.immuni.2016.06.013. Epub 2016 Jul 12.

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

Author information

1
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA. Electronic address: hamletchu.berkeley@gmail.com.
2
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
3
Departments of Statistics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK.
4
Center of Pathophysiology of Toulouse-Purpan, INSERM UMR1043-CNRS UMR5282, University of Toulouse, 31024 Toulouse Cedex 3, France.
5
Applied Mathematics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK.
6
Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA. Electronic address: erobey@berkeley.edu.

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-2L(d), 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.

PMID:
27421704
PMCID:
PMC4956557
DOI:
10.1016/j.immuni.2016.06.013
[Indexed for MEDLINE]
Free PMC Article

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