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

McNally, Alice, McNally, Michael, Galea, Ryan, Thomas, Ranjeny and Steptoe, Raymond J. (2014) Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+T-cell effector differentiation by IL-2 modulation. PloS One, 9 1: . doi:10.1371/journal.pone.0085455


Author McNally, Alice
McNally, Michael
Galea, Ryan
Thomas, Ranjeny
Steptoe, Raymond J.
Title Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+T-cell effector differentiation by IL-2 modulation
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-01-13
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pone.0085455
Open Access Status DOI
Volume 9
Issue 1
Total pages 9
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
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+ Tcell differentiation under steady-state conditions.
Keyword Dendritic cells
Peripheral tolerance
In vivo
Autoimmunity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e85455

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
 
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