CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis

McNally, Alice, Hill, Geoffrey R., Sparwasser, Tim, Thomas, Ranjeny and Steptoe, Raymond J. (2011) CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis. Proceedings of the National Academy of Sciences of the United States of America, 108 18: 7529-7534. doi:10.1073/pnas.1103782108

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Author McNally, Alice
Hill, Geoffrey R.
Sparwasser, Tim
Thomas, Ranjeny
Steptoe, Raymond J.
Title CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis
Formatted title
CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2011-05-03
Sub-type Article (original research)
DOI 10.1073/pnas.1103782108
Open Access Status File (Author Post-print)
Volume 108
Issue 18
Start page 7529
End page 7534
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2012
Language eng
Formatted abstract
CD4+CD25+ regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms of Treg suppression in vitro have been described, the mechanisms by which Treg modulate CD8+ T cell differentiation and effector function in vivo are more poorly defined. It has been proposed, in many instances, that modulation of cytokine homeostasis could be an important mechanism by which Treg regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate that CD4+CD25+ Treg, by critically regulating IL-2 homeostasis, modulate CD8+ T-cell effector differentiation. Expansion and effector differentiation of CD8+ T cells is promoted by autocrine IL-2 but, by competing for IL-2, Treg limit CD8+ effector differentiation. Furthermore, a regulatory loop exists between Treg and CD8+ effector T cells, where IL-2 produced during CD8+ T-cell effector differentiation promotes Treg expansion.
Keyword Treg
Immune responses
Effector function
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Tue, 20 Sep 2011, 14:04:24 EST by Professor Ranjeny Thomas on behalf of Institute for Molecular Bioscience