Cargando…

An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12

The proinflammatory cytokine IL-12 drives the generation of terminally differentiated KLRG1(+) effector CD8(+) T cells. Using a Toxoplasma vaccination model, we delineate the sequence of events that naïve CD8(+) T cells undergo to become terminal effectors and the differentiation steps controlled by...

Descripción completa

Detalles Bibliográficos
Autores principales: Shah, Suhagi, Grotenbreg, Gijsbert M, Rivera, Amariliz, Yap, George S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549662/
https://www.ncbi.nlm.nih.gov/pubmed/26244629
http://dx.doi.org/10.7554/eLife.09017
_version_ 1782387346176475136
author Shah, Suhagi
Grotenbreg, Gijsbert M
Rivera, Amariliz
Yap, George S
author_facet Shah, Suhagi
Grotenbreg, Gijsbert M
Rivera, Amariliz
Yap, George S
author_sort Shah, Suhagi
collection PubMed
description The proinflammatory cytokine IL-12 drives the generation of terminally differentiated KLRG1(+) effector CD8(+) T cells. Using a Toxoplasma vaccination model, we delineate the sequence of events that naïve CD8(+) T cells undergo to become terminal effectors and the differentiation steps controlled by IL-12. We demonstrate that direct IL-12 signaling on CD8(+) T cells is essential for the induction of KLRG1 and IFN-γ, but the subsequent downregulation of CXCR3 is controlled by IL-12 indirectly through the actions of IFN-γ and IFN-γ-inducible chemokines. Differentiation of nascent effectors occurs in an extrafollicular splenic compartment and is driven by late IL-12 production by DCs distinct from the classical CD8α(+) DC. Unexpectedly, we also found extensive proliferation of both KLRG1(−) and KLRG1(+) CD8(+) T cells in the marginal zone and red pulp, which ceases prior to the final KLRG1(Hi) CXCR3(Lo) stage. Our findings highlight the notion of an extrafollicular pathway for effector T cell generation. DOI: http://dx.doi.org/10.7554/eLife.09017.001
format Online
Article
Text
id pubmed-4549662
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-45496622015-08-26 An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12 Shah, Suhagi Grotenbreg, Gijsbert M Rivera, Amariliz Yap, George S eLife Immunology The proinflammatory cytokine IL-12 drives the generation of terminally differentiated KLRG1(+) effector CD8(+) T cells. Using a Toxoplasma vaccination model, we delineate the sequence of events that naïve CD8(+) T cells undergo to become terminal effectors and the differentiation steps controlled by IL-12. We demonstrate that direct IL-12 signaling on CD8(+) T cells is essential for the induction of KLRG1 and IFN-γ, but the subsequent downregulation of CXCR3 is controlled by IL-12 indirectly through the actions of IFN-γ and IFN-γ-inducible chemokines. Differentiation of nascent effectors occurs in an extrafollicular splenic compartment and is driven by late IL-12 production by DCs distinct from the classical CD8α(+) DC. Unexpectedly, we also found extensive proliferation of both KLRG1(−) and KLRG1(+) CD8(+) T cells in the marginal zone and red pulp, which ceases prior to the final KLRG1(Hi) CXCR3(Lo) stage. Our findings highlight the notion of an extrafollicular pathway for effector T cell generation. DOI: http://dx.doi.org/10.7554/eLife.09017.001 eLife Sciences Publications, Ltd 2015-08-05 /pmc/articles/PMC4549662/ /pubmed/26244629 http://dx.doi.org/10.7554/eLife.09017 Text en © 2015, Shah et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology
Shah, Suhagi
Grotenbreg, Gijsbert M
Rivera, Amariliz
Yap, George S
An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12
title An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12
title_full An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12
title_fullStr An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12
title_full_unstemmed An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12
title_short An extrafollicular pathway for the generation of effector CD8(+) T cells driven by the proinflammatory cytokine, IL-12
title_sort extrafollicular pathway for the generation of effector cd8(+) t cells driven by the proinflammatory cytokine, il-12
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549662/
https://www.ncbi.nlm.nih.gov/pubmed/26244629
http://dx.doi.org/10.7554/eLife.09017
work_keys_str_mv AT shahsuhagi anextrafollicularpathwayforthegenerationofeffectorcd8tcellsdrivenbytheproinflammatorycytokineil12
AT grotenbreggijsbertm anextrafollicularpathwayforthegenerationofeffectorcd8tcellsdrivenbytheproinflammatorycytokineil12
AT riveraamariliz anextrafollicularpathwayforthegenerationofeffectorcd8tcellsdrivenbytheproinflammatorycytokineil12
AT yapgeorges anextrafollicularpathwayforthegenerationofeffectorcd8tcellsdrivenbytheproinflammatorycytokineil12
AT shahsuhagi extrafollicularpathwayforthegenerationofeffectorcd8tcellsdrivenbytheproinflammatorycytokineil12
AT grotenbreggijsbertm extrafollicularpathwayforthegenerationofeffectorcd8tcellsdrivenbytheproinflammatorycytokineil12
AT riveraamariliz extrafollicularpathwayforthegenerationofeffectorcd8tcellsdrivenbytheproinflammatorycytokineil12
AT yapgeorges extrafollicularpathwayforthegenerationofeffectorcd8tcellsdrivenbytheproinflammatorycytokineil12