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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3890313?pdf=render |
| _version_ | 1818289610817536000 |
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| author | Alice McNally Michael McNally Ryan Galea Ranjeny Thomas Raymond J Steptoe |
| author_facet | Alice McNally Michael McNally Ryan Galea Ranjeny Thomas Raymond J Steptoe |
| author_sort | Alice McNally |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T02:15:01Z |
| format | Article |
| id | doaj.art-d2f07febd25e4f84ad09481706d8b7a6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T02:15:01Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d2f07febd25e4f84ad09481706d8b7a62022-12-22T00:02:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8545510.1371/journal.pone.0085455Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation.Alice McNallyMichael McNallyRyan GaleaRanjeny ThomasRaymond J SteptoeAbsorption 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.http://europepmc.org/articles/PMC3890313?pdf=render |
| spellingShingle | Alice McNally Michael McNally Ryan Galea Ranjeny Thomas Raymond J Steptoe Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation. PLoS ONE |
| title | Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation. |
| title_full | Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation. |
| title_fullStr | Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation. |
| title_full_unstemmed | Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation. |
| title_short | Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation. |
| title_sort | immunogenic but not steady state antigen presentation permits regulatory t cells to control cd8 t cell effector differentiation by il 2 modulation |
| url | http://europepmc.org/articles/PMC3890313?pdf=render |
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