Differentiation, Distribution and γδ T Cell-Driven Regulation of IL-22-Producing T Cells in Tuberculosis

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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 Vγ2Vδ2 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 IFNγ-producing Vγ2Vδ2 T effector cells after HMBPP stimulation coincided with the down-regulated capacity of these T cells to produce IL-22 de novo. Importantly, anti-IFNγ neutralizing Ab treatment reversed the HMBPP-mediated down-regulation effect on IL-22-producing T cells, suggesting that Vγ2Vδ2 T-cell-driven IFNγ-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 Vγ2Vδ2 T cells for balancing potentially hyper-activating IL-22-producing T cells in severe TB.

Vyšlo v časopise: Differentiation, Distribution and γδ T Cell-Driven Regulation of IL-22-Producing T Cells in Tuberculosis. PLoS Pathog 6(2): e32767. doi:10.1371/journal.ppat.1000789
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000789

Souhrn

Zdroje

1. ZenewiczLA

YancopoulosGD

ValenzuelaDM

MurphyAJ

StevensS

2008 Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29 947 957

2. WolkK

SabatR

2006 Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the biology of tissue cells. Cytokine Growth Factor Rev 17 367 380

3. ZenewiczLA

YancopoulosGD

ValenzuelaDM

MurphyAJ

KarowM

2007 Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27 647 659

4. WolkK

KunzS

WitteE

FriedrichM

AsadullahK

2004 IL-22 increases the innate immunity of tissues. Immunity 21 241 254

5. LiangSC

TanXY

LuxenbergDP

KarimR

Dunussi-JoannopoulosK

2006 Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203 2271 2279

6. AujlaSJ

ChanYR

ZhengM

FeiM

AskewDJ

2008 IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 14 275 281

7. ZhengY

ValdezPA

DanilenkoDM

HuY

SaSM

2008 Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14 282 289

8. ZhengY

DanilenkoDM

ValdezP

KasmanI

Eastham-AndersonJ

2007 Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445 648 651

9. MaHL

LiangS

LiJ

NapierataL

BrownT

2008 IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 118 597 607

10. KhaderSA

BellGK

PearlJE

FountainJJ

Rangel-MorenoJ

2007 IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 8 369 377

11. NorthRJ

JungYJ

2004 Immunity to tuberculosis. Annu Rev Immunol 22 599 623

12. FlynnJL

ChanJ

2001 Immunology of tuberculosis. Annu Rev Immunol 19 93 129

13. LockhartE

GreenAM

FlynnJL

2006 IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol 177 4662 4669

14. QiuL

HuangD

ChenCY

WangR

ShenL

2008 Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1alpha, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-beta, TIM1, and TLR2 but low antigen-specific cellular responses. J Infect Dis 198 1514 1519

15. ScribaTJ

KalsdorfB

AbrahamsDA

IsaacsF

HofmeisterJ

2008 Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol 180 1962 1970

16. ChenZW

2005 Immune regulation of gammadelta T cell responses in mycobacterial infections. Clin Immunol 116 202 207

17. SicardH

IngoureS

LucianiB

SerrazC

FournieJJ

2005 In vivo immunomanipulation of V gamma 9V delta 2 T cells with a synthetic phosphoantigen in a preclinical nonhuman primate model. J Immunol 175 5471 5480

18. OttonesF

DornandJ

NaroeniA

LiautardJP

FaveroJ

2000 V gamma 9V delta 2 T cells impair intracellular multiplication of Brucella suis in autologous monocytes through soluble factor release and contact-dependent cytotoxic effect. J Immunol 165 7133 7139

19. PocciaF

AgratiC

MartiniF

CapobianchiMR

WallaceM

2005 Antiviral reactivities of gammadelta T cells. Microbes Infect 7 518 528

20. PocciaF

BattistiniL

CiprianiB

MancinoG

MartiniF

1999 Phosphoantigen-reactive Vgamma9Vdelta2 T lymphocytes suppress in vitro human immunodeficiency virus type 1 replication by cell-released antiviral factors including CC chemokines. J Infect Dis 180 858 861

21. ShenY

ZhouD

QiuL

LaiX

SimonM

2002 Adaptive immune response of Vgamma2Vdelta2+ T cells during mycobacterial infections. Science 295 2255 2258

22. WangL

KamathA

DasH

LiL

BukowskiJF

2001 Antibacterial effect of human V gamma 2V delta 2 T cells in vivo. J Clin Invest 108 1349 1357

23. SpencerCT

AbateG

BlazevicA

HoftDF

2008 Only a subset of phosphoantigen-responsive gamma9delta2 T cells mediate protective tuberculosis immunity. J Immunol 181 4471 4484

24. HintzM

ReichenbergA

AltincicekB

BahrU

GschwindRM

2001 Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human gammadelta T cells in Escherichia coli. FEBS Lett 509 317 322

25. TanakaY

MoritaCT

TanakaY

NievesE

BrennerMB

1995 Natural and synthetic non-peptide antigens recognized by human gamma delta T cells. Nature 375 155 158

26. AltincicekB

MollJ

CamposN

FoersterG

BeckE

2001 Cutting edge: human gamma delta T cells are activated by intermediates of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis. J Immunol 166 3655 3658

27. BelmantC

EspinosaE

PoupotR

PeyratMA

GuiraudM

1999 3-Formyl-1-butyl pyrophosphate A novel mycobacterial metabolite-activating human gammadelta T cells. J Biol Chem 274 32079 32084

28. WeiH

HuangD

LaiX

ChenM

ZhongW

2008 Definition of APC presentation of phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate to Vgamma2Vdelta 2 TCR. J Immunol 181 4798 4806

29. AliZ

ShaoL

HallidayL

ReichenbergA

HintzM

2007 Prolonged (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate-driven antimicrobial and cytotoxic responses of pulmonary and systemic Vgamma2Vdelta2 T cells in macaques. J Immunol 179 8287 8296

30. GongG

ShaoL

WangY

ChenCY

HuangD

2009 Phosphoantigen-activated V{gamma}2V{delta}2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection. Blood 113 837 845

31. HuangD

ShenY

QiuL

ChenCY

ShenL

2008 Immune distribution and localization of phosphoantigen-specific Vgamma2Vdelta2 T cells in lymphoid and nonlymphoid tissues in Mycobacterium tuberculosis infection. Infect Immun 76 426 436

32. ChenCY

HuangD

WangRC

ShenL

ZengG

2009 A Critical Role for CD8 T cells in a Nonhuman Primate Model of Tuberculosis. PLoS Pathog 5 1000392 doi:10.1371/journal.ppat.1000392

33. ChenY

ShaoL

AliZ

CaiJ

ChenZW

2008 NSOM/QD-based nanoscale immunofluorescence imaging of antigen-specific T-cell receptor responses during an in vivo clonal V{gamma}2V{delta}2 T-cell expansion. Blood 111 4220 4232

34. SanchezFO

RodriguezJI

AgudeloG

GarciaLF

1994 Immune responsiveness and lymphokine production in patients with tuberculosis and healthy controls. Infect Immun 62 5673 5678

35. ZhangM

LinY

IyerDV

GongJ

AbramsJS

1995 T-cell cytokine responses in human infection with Mycobacterium tuberculosis. Infect Immun 63 3231 3234

36. GongJH