The longevity of memory CD8 T cell responses after repetitive antigen stimulations

Deepa Rai; Matthew D Martin; Vladimir P Badovinac

doi:10.4049/jimmunol.1301063

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The longevity of memory CD8 T cell responses after repetitive antigen stimulations

Journal article

Peer reviewed

The longevity of memory CD8 T cell responses after repetitive antigen stimulations

Deepa Rai, Matthew D Martin and Vladimir P Badovinac

The Journal of immunology (1950), Vol.192(12), pp.5652-5659

06/15/2014

DOI: 10.4049/jimmunol.1301063

PMCID: PMC4127884

PMID: 24829415

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Abstract

In experimental models in which the Ag-stimulation history of memory CD8 T cell populations was clearly defined (adoptive transfer of a known number of TCR-transgenic memory CD8 T cells), all facets of the ensuing CD8 T cell responses, including proliferative expansion, duration and extent of contraction, diversification of memory CD8 T cell transcriptomes, and life-long survival, were dependent on the number of prior Ag encounters. However, the extent to which sequential adoptive-transfer models reflect the physiological scenario in which memory CD8 T cells are generated by repetitive Ag challenges of individual hosts (no adoptive transfer involved) is not known. Direct comparison of endogenous memory CD8 T cell responses generated in repetitively infected hosts revealed that recurrent homologous boosting was required to preserve the numbers and increase the phenotypic and functional complexity of the developing memory CD8 T cell pool. Although life-long survival of the memory CD8 T cells was not impacted, phenotype (i.e., upregulation of CD62L) and function (i.e., homeostatic turnover, Ag-stimulated IL-2 production) of repeatedly stimulated memory CD8 T cells were dependent on time after last Ag encounter. Therefore, repetitive Ag challenges of individual hosts can substantially influence the numerical and functional attributes of polyclonal memory CD8 T cells, a notion with important implications for the design of future vaccination strategies aimed at increasing the number of protective memory CD8 T cells.

Immunologic Memory - physiology

CD8-Positive T-Lymphocytes - cytology

Interleukin-2 - genetics

Animals

Interleukin-2 - immunology

Time Factors

Antigens, Bacterial - immunology

Cell Survival - genetics

Mice, Transgenic

Mice

CD8-Positive T-Lymphocytes - immunology

Cell Survival - immunology

Details

Title: Subtitle: The longevity of memory CD8 T cell responses after repetitive antigen stimulations
Creators: Deepa Rai - Department of Pathology, University of Iowa, Iowa City, IA 52242; and
Matthew D Martin - Department of Pathology, University of Iowa, Iowa City, IA 52242; and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242
Vladimir P Badovinac - Department of Pathology, University of Iowa, Iowa City, IA 52242; and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 vladimir-badovinac@uiowa.edu
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.192(12), pp.5652-5659
DOI: 10.4049/jimmunol.1301063
PMID: 24829415
PMCID: PMC4127884
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI83286 / NIAID NIH HHS P30CA086862 / NCI NIH HHS R21 AI096850 / NIAID NIH HHS R01 AI083286 / NIAID NIH HHS AI96850 / NIAID NIH HHS
Language: English
Date published: 06/15/2014
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984046826602771

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