Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation

PLoS One. 2014 Jan 13;9(1):e85455. doi: 10.1371/journal.pone.0085455. eCollection 2014.

Abstract

Absorption of IL-2 is one proposed mechanism of CD4+CD25+FoxP3+ regulatory T cell (Treg) suppression. Direct in vivo experimental evidence for this has recently been obtained. While modulation of IL-2 bioavailability controls CD8+ T-cell effector differentiation under strongly immunogenic conditions it is not known whether Treg modulate CD8+ T cell responses through this mechanism under steady-state conditions. Here we assess this using a mouse model in which dendritic cells (DC) are manipulated to present cognate antigen to CD8+ T cells either in the steady-state or after activation. Our observations show that Treg exert a check on expansion and effector differentiation of CD8+ T cells under strongly immunogenic conditions associated with TLR ligand activation of DC, and this is mediated by limiting IL-2 availability. In contrast, when DC remain unactivated, depletion of Treg has little apparent effect on effector differentiation or IL-2 homeostasis. We conclude that while modulation of IL-2 homeostasis is an important mechanism through which Treg control CD8+ effector differentiation under immunogenic conditions, this mechanism plays little role in modulating CD8+ T-cell differentiation under steady-state conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Dendritic Cells / immunology
  • Homeostasis
  • Interleukin-2 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Interleukin-2

Grants and funding

This work was supported by the National Health and Medical Research Council (project #1013066). www.nhmrc.gov.au. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.