Differentiation, distribution and gammadelta T cell-driven regulation of IL-22-producing T cells in tuberculosis.
Differentiation, distribution and immune regulation of human IL-22-producing T cells in infections remain unknown. Here, we demonstrated in a nonhuman primate model that M. tuberculosis infection resulted in apparent increases in numbers of T cells capable of producing IL-22 de novo without in vitro...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2010-02-01
|
Series: | PLoS Pathogens |
Online Access: | http://europepmc.org/articles/PMC2829073?pdf=render |
id |
doaj-4c58817a605d4388865c90d852664d51 |
---|---|
record_format |
Article |
spelling |
doaj-4c58817a605d4388865c90d852664d512020-11-25T02:38:52ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-02-0162e100078910.1371/journal.ppat.1000789Differentiation, distribution and gammadelta T cell-driven regulation of IL-22-producing T cells in tuberculosis.Shuyu YaoDan HuangCrystal Y ChenLisa HallidayGucheng ZengRichard C WangZheng W ChenDifferentiation, distribution and immune regulation of human IL-22-producing T cells in infections remain unknown. Here, we demonstrated in a nonhuman primate model that M. tuberculosis infection resulted in apparent increases in numbers of T cells capable of producing IL-22 de novo without in vitro Ag stimulation, and drove distribution of these cells more dramatically in lungs than in blood and lymphoid tissues. Consistently, IL-22-producing T cells were visualized in situ in lung tuberculosis (TB) granulomas by confocal microscopy and immunohistochemistry, indicating that mature IL-22-producing T cells were present in TB granuloma. Surprisingly, phosphoantigen HMBPP activation of Vgamma2Vdelta2 T cells down-regulated the capability of T cells to produce IL-22 de novo in lymphocytes from blood, lung/BAL fluid, spleen and lymph node. Up-regulation of IFNgamma-producing Vgamma2Vdelta2 T effector cells after HMBPP stimulation coincided with the down-regulated capacity of these T cells to produce IL-22 de novo. Importantly, anti-IFNgamma neutralizing Ab treatment reversed the HMBPP-mediated down-regulation effect on IL-22-producing T cells, suggesting that Vgamma2Vdelta2 T-cell-driven IFNgamma-networking function was the mechanism underlying the HMBPP-mediated down-regulation of the capability of T cells to produce IL-22. These novel findings raise the possibility to ultimately investigate the function of IL-22 producing T cells and to target Vgamma2Vdelta2 T cells for balancing potentially hyper-activating IL-22-producing T cells in severe TB.http://europepmc.org/articles/PMC2829073?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuyu Yao Dan Huang Crystal Y Chen Lisa Halliday Gucheng Zeng Richard C Wang Zheng W Chen |
spellingShingle |
Shuyu Yao Dan Huang Crystal Y Chen Lisa Halliday Gucheng Zeng Richard C Wang Zheng W Chen Differentiation, distribution and gammadelta T cell-driven regulation of IL-22-producing T cells in tuberculosis. PLoS Pathogens |
author_facet |
Shuyu Yao Dan Huang Crystal Y Chen Lisa Halliday Gucheng Zeng Richard C Wang Zheng W Chen |
author_sort |
Shuyu Yao |
title |
Differentiation, distribution and gammadelta T cell-driven regulation of IL-22-producing T cells in tuberculosis. |
title_short |
Differentiation, distribution and gammadelta T cell-driven regulation of IL-22-producing T cells in tuberculosis. |
title_full |
Differentiation, distribution and gammadelta T cell-driven regulation of IL-22-producing T cells in tuberculosis. |
title_fullStr |
Differentiation, distribution and gammadelta T cell-driven regulation of IL-22-producing T cells in tuberculosis. |
title_full_unstemmed |
Differentiation, distribution and gammadelta T cell-driven regulation of IL-22-producing T cells in tuberculosis. |
title_sort |
differentiation, distribution and gammadelta t cell-driven regulation of il-22-producing t cells in tuberculosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2010-02-01 |
description |
Differentiation, distribution and immune regulation of human IL-22-producing T cells in infections remain unknown. Here, we demonstrated in a nonhuman primate model that M. tuberculosis infection resulted in apparent increases in numbers of T cells capable of producing IL-22 de novo without in vitro Ag stimulation, and drove distribution of these cells more dramatically in lungs than in blood and lymphoid tissues. Consistently, IL-22-producing T cells were visualized in situ in lung tuberculosis (TB) granulomas by confocal microscopy and immunohistochemistry, indicating that mature IL-22-producing T cells were present in TB granuloma. Surprisingly, phosphoantigen HMBPP activation of Vgamma2Vdelta2 T cells down-regulated the capability of T cells to produce IL-22 de novo in lymphocytes from blood, lung/BAL fluid, spleen and lymph node. Up-regulation of IFNgamma-producing Vgamma2Vdelta2 T effector cells after HMBPP stimulation coincided with the down-regulated capacity of these T cells to produce IL-22 de novo. Importantly, anti-IFNgamma neutralizing Ab treatment reversed the HMBPP-mediated down-regulation effect on IL-22-producing T cells, suggesting that Vgamma2Vdelta2 T-cell-driven IFNgamma-networking function was the mechanism underlying the HMBPP-mediated down-regulation of the capability of T cells to produce IL-22. These novel findings raise the possibility to ultimately investigate the function of IL-22 producing T cells and to target Vgamma2Vdelta2 T cells for balancing potentially hyper-activating IL-22-producing T cells in severe TB. |
url |
http://europepmc.org/articles/PMC2829073?pdf=render |
work_keys_str_mv |
AT shuyuyao differentiationdistributionandgammadeltatcelldrivenregulationofil22producingtcellsintuberculosis AT danhuang differentiationdistributionandgammadeltatcelldrivenregulationofil22producingtcellsintuberculosis AT crystalychen differentiationdistributionandgammadeltatcelldrivenregulationofil22producingtcellsintuberculosis AT lisahalliday differentiationdistributionandgammadeltatcelldrivenregulationofil22producingtcellsintuberculosis AT guchengzeng differentiationdistributionandgammadeltatcelldrivenregulationofil22producingtcellsintuberculosis AT richardcwang differentiationdistributionandgammadeltatcelldrivenregulationofil22producingtcellsintuberculosis AT zhengwchen differentiationdistributionandgammadeltatcelldrivenregulationofil22producingtcellsintuberculosis |
_version_ |
1724789223102349312 |