Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation.
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.
UQ Diamantina Institute, University of Queensland, Brisbane, Australia.
Alice
A
McNally
UQ Diamantina Institute, University of Queensland, Brisbane, Australia.
Michael
M
McNally
UQ Diamantina Institute, University of Queensland, Brisbane, Australia.
Ryan
R
Galea
UQ Diamantina Institute, University of Queensland, Brisbane, Australia.
Ranjeny
R
Thomas
UQ Diamantina Institute, University of Queensland, Brisbane, Australia.
Raymond J
RJ
Steptoe
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D006706:Homeostasis; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007376:Interleukin-2