Journal article
The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses
PLoS pathogens, Vol.11(10), pp.e1005199-e1005199
10/2015
DOI: 10.1371/journal.ppat.1005199
PMCID: PMC4592272
PMID: 26431533
Abstract
Memory CD8 T cells provide protection to immune hosts by eliminating pathogen-infected cells during re-infection. While parameters influencing the generation of primary (1°) CD8 T cells are well established, the factors controlling the development of secondary (2°) CD8 T cell responses remain largely unknown. Here, we address the mechanisms involved in the generation and development of 2° memory (M) CD8 T cells. We observed that the time at which 1° M CD8 T cells enter into immune response impacts their fate and differentiation into 2° M CD8 T cells. Late-entry of 1° M CD8 T cells into an immune response (relative to the onset of infection) not only facilitated the expression of transcription factors associated with memory formation in 2° effector CD8 T cells, but also influenced the ability of 2° M CD8 T cells to localize within the lymph nodes, produce IL-2, and undergo Ag-driven proliferation. The timing of stimulation of 1° M CD8 T cells also impacted the duration of expression of the high-affinity IL-2 receptor (CD25) on 2° effector CD8 T cells and their sensitivity to IL-2 signaling. Importantly, by blocking or enhancing IL-2 signaling in developing 2° CD8 T cells, we provide direct evidence for the role of IL-2 in controlling the differentiation of Ag-driven 2° CD8 T cell responses. Thus, our data suggest that the process of 1° M to 2° M CD8 T cell differentiation is not fixed and can be manipulated, a notion with relevance for the design of future prime-boost vaccination approaches.
Details
- Title: Subtitle
- The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses
- Creators
- Shaniya H Khan - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of AmericaMatthew D Martin - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of AmericaGabriel R Starbeck-Miller - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of AmericaHai-Hui Xue - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America; Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of AmericaJohn T Harty - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America; Department of Microbiology, University of Iowa, Iowa City, Iowa, United States of America; Department of Pathology, University of Iowa, Iowa City, Iowa, United States of AmericaVladimir P Badovinac - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America; Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.11(10), pp.e1005199-e1005199
- DOI
- 10.1371/journal.ppat.1005199
- PMID
- 26431533
- PMCID
- PMC4592272
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Publisher
- Public Library of Science; United States
- Grant note
- R01 AI114543 / NIAID NIH HHS AI114543 / NIAID NIH HHS R21 AI119160 / NIAID NIH HHS
- Language
- English
- Date published
- 10/2015
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047725702771
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