Th17/Treg imbalance in malignant pleural effusion

Abstract

Both T helper IL-17-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in malignant pleural effusion (MPE). However, the possible imbalance between Th17 cells and Tregs, as well as the association of Th17/Treg and Th1/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as Th1/Th2 balance in MPE. The number of Th17, Tregs, Th1, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Th17, Tregs, Th1, and Th2 cells was explored. It was found that the number of Th17, Tregs, Th1, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Th17 cells was correlated negatively with Tregs in MPE, but not in blood. Th17 cells and Th17/Treg ratio were positively, and Tregs were negatively, correlated with Th1 cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Th17 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Th17/Treg imbalance exists in MPE.

Keywords

malignant pleural effusion / regulatory T cells / Th17 cells / Th1/Th2 imbalance

References

[1] LightR.W.. Clinical practice. Pleural effusion. N Engl J Med, 2002, 346(25): 1971-1977

[2] LuciveroG., PierucciG., BonomoL.. Lymphocyte subsets in peripheral blood and pleural fluid. Eur Respir J, 1988, 1(4): 337-340

[3] AtanackovicD., BlockA., deW.A., et al.. Characterization of effusion-infiltrating T cells: benign versus malignant effusions. Clin Cancer Res, 2004, 10(8): 2600-2608

[4] FontenotJ.D., GavinM.A., RudenskyA.Y.. Foxp3 programs the development and function of CD4⁺CD25⁺ regulatory T cells. Nat Immunol, 2003, 4(4): 330-336

[5] MillsK.H.. Induction, function and regulation of IL-17-producing T cells. Eur J Immunol, 2008, 38(10): 2636-2649

[6] ChenY.Q., ShiH.Z., QinX.J., et al.. CD4+CD25+ regulatory T lymphocytes in malignant pleural effusion. Am J Respir Crit Care Med, 2005, 172(11): 1434-1439

[7] QinX.J., ShiH.Z., LiangQ.L., et al.. CCL22 recruits CD4-positive CD25-positive regulatory T cells into malignant pleural effusion. Clin Cancer Res, 2009, 15(7): 2231-2237

[8] YeZ.J., ZhouQ., GuY.Y., et al.. Generation and differentiation of interleukin-17-producing CD4+ T cells in malignant pleural effusion. J Immunol, 2010, 185(10): 6348-6354

[9] QinX.J., ShiH.Z., HuangZ.X., et al.. Interleukin-16 in tuberculous and malignant pleural effusions. Eur Respir J, 2005, 25(4): 605-611

[10] AntonyV.B.. Immunological mechanisms in pleural disease. Eur Respir J, 2003, 21(3): 539-544

[11] DalbethN., LeeY.C.. Lymphocytes in pleural disease. Curr Opin Pulm Med, 2005, 11(4): 334-339

[12] VolpeE., ServantN., ZollingerR., et al.. A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses. Nat Immunol, 2008, 9(6): 650-657

[13] BeriouG., CostantinoC.M., AshleyC.W., et al.. IL-17-producing human peripheral regulatory T cells retain suppressive function. Blood, 2009, 113(18): 4240-4249

[14] VooK.S., WangY.H., SantoriF.R., et al.. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci U S A, 2009, 106(12): 4793-4798

[15] AyyoubM., DeknuydtF., RaimbaudI., et al.. Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the TH17 lineage-specific transcription factor RORγt. Proc Natl Acad Sci U S A, 2009, 106(21): 8635-8640

[16] BettelliE., CarrierY., GaoW., et al.. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature, 2006, 441(7090): 235-238

[17] VeldhoenM., HockingR.J., AtkinsC.J., et al.. TGF-β in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity, 2006, 24(2): 179-189

[18] OshikawaK., YanagisawaK., OhnoS., et al.. Expression of ST2 in helper T lymphocytes of malignant pleural effusions. Am J Respir Crit Care Med, 2002, 165(7): 1005-1009

[19] ChenY.M., YangW.K., Whang-PengJ., et al.. Elevation of interleukin-10 levels in malignant pleural effusion. Chest, 1996, 110(2): 433-436

[20] SatoM., GotoS., KanekoR., et al.. Impaired production of Th1 cytokines and increased frequency of Th2 subsets in PBMC from advanced cancer patients. Anticancer Res, 1998, 18(5D): 3951-3955

[21] OkamotoM., HasegawaY., HaraT., et al.. T-helper type 1/T-helper type 2 balance in malignant pleural effusions compared to tuberculous pleural effusions. Chest, 2005, 128(6): 4030-4035

[22] KryczekI., BruceA.T., GudjonssonJ.E., et al.. Induction of IL-17+ T cell trafficking and development by IFN-γ: mechanism and pathological relevance in psoriasis. J Immunol, 2008, 181(7): 4733-4741

[23] WeaverC.T., HattonR.D.. Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nat Rev Immunol, 2009, 9(12): 883-889