Il10 Inversely Correlates With The Percentage Of Cd8+ Cells In Mds Patients

The role of the immune system in myelodysplastic syndrome (MDS) progression has been widely accepted, although mechanisms underlying this immune dysfunction are not clear. CD4+ and CD8+ lymphocyte profiles in the peripheral blood of MDS patients were evaluated and correlated with clinical characteristics, the expression of FOXP3 and the anti-inflammatory cytokines IL10, TGFβ1 and CTLA4. IL10 expression inversely correlated with the percentage of CD8+ cells and was higher in high-risk MDS. Our findings provide further evidence for the role of T cell-mediated IL10 production in MDS and strengthen the idea of distinct cytokine profiles in low and high-risk MDS. © 2013 Elsevier Ltd.375541546Deeg, H.J., Beckham, C., Loken, M.R., Bryant, E., Lesnikova, M., Shulman, H.M., Gooley, T., Negative regulators of hemopoiesis and stroma function in patients with myelodysplastic syndrome (2000) Leuk Lymphoma, 37, pp. 405-414Mufti, G., List, A.F., Gore, S.D., Ho, A.Y., Myelodysplastic syndrome (2003) Hematology Am Soc Hematol Educ Program, pp. 176-199Parker, J.E., Mufti, G.J., Ineffective hematopoiesis and apoptosis in myelodysplastic syndromes (1998) Br J Haematol, 101, pp. 220-230Parker, J.E., Mufti, G.J., Excessive apoptosis in low risk myelodysplastic syndromes (MDS) (2000) Leuk Lymphoma, 40, pp. 1-24Parker, J.E., Mufti, G.J., Rasool, F., Mijovic, A., Devereux, S., Pagliuca, A., The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS (2000) Blood, 96, pp. 3932-3938Barrett, A.J., Sloand, E., Autoimmune mechanisms in the pathophysiology of myelodysplastic syndromes and their clinical relevance (2009) Haematologica, 94, pp. 449-451Aggarwal, S., van de Loosdrecht, A.A., Alhan, C., Ossenkoppele, G.J., Westers, T.M., Bontkes, H.J., Role of immune responses in the pathogenesis of low-risk MDS and high-risk MDS: implications for immunotherapy (2011) Br J Haematol, 153, pp. 568-581Kotsianidis, I., Bouchliou, I., Nakou, E., Spanoudakis, E., Margaritis, D., Christophoridou, A.V., Anastasiades, A., Tsatalas, C., Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS) (2009) Leukemia, 23, pp. 510-518Ortega, J., List, A., Immunomodulatory drugs in the treatment of myelodysplastic syndromes (2007) Curr Opin Oncol, 19, pp. 656-659Greenberg, P.L., Young, N.S., Gattermann, N., Myelodysplastic syndromes (2002) Hematology Am Soc Hematol Educ Program, pp. 136-161Molldrem, J.J., Caples, M., Mavroudis, D., Plante, M., Young, N.S., Barrett, A.J., Antithymocyte globulin for patients with myelodysplastic syndrome (1997) Br J Haematol, 99, pp. 699-705Killick, S.B., Mufti, G., Cavenagh, J.D., Mijovic, A., Peacock, J.L., Gordon-Smith, E.C., Bowen, D.T., Marsh, J.C., A pilot study of antithymocyte globulin (ATG) in the treatment of patients with 'low-risk' myelodysplasia (2003) Br J Haematol, 120, pp. 679-684Fozza, C., Longinotti, M., Are T-cell dysfunctions the other side of the moon in the pathogenesis of myelodysplastic syndromes? (2012) Eur J Haematol, 88, pp. 380-387Kordasti, S.Y., Ingram, W., Hayden, J., Darling, D., Barber, L., Afzali, B., Lombardi, G., Mufti, G.J., CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS) (2007) Blood, 110, pp. 847-850Zou, J.X., Rollison, D.E., Boulware, D., Chen, D.T., Sloand, E.M., Pfannes, L.V., Goronzy, J.J., Epling-Burnette, P.K., Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome (2009) Leukemia, 23, pp. 1288-1296Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method (2001) Methods, 25, pp. 402-408Tabachnick, B.G., Fidell, L.S., (2001) Using Multivariate Statistics, pp. 111-176. , Allyn and Bacon, BostonYoshida, Y., Stephenson, J., Mufti, G.J., Myelodysplastic syndromes: from morphology to molecular biology. Part I. Classification, natural history and cell biology of myelodysplasia (1993) Int J Hematol, 57, pp. 87-97Bogdanovic, A.D., Trpinac, D.P., Jankovic, G.M., Bumbasirevic, V.Z., Obradovic, M., Colovic, M.D., Incidence and role of apoptosis in myelodysplastic syndrome: morphological and ultrastructural assessment (1997) Leukemia, 11, pp. 656-659Nilsson, L., Astrand-Grundstrom, I., Arvidsson, I., Jacobsson, B., Hellstrom-Lindberg, E., Hast, R., Jacobsen, S.E., Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level (2000) Blood, 96, pp. 2012-2021Shioi, Y., Tamura, H., Yokose, N., Satoh, C., Dan, K., Ogata, K., Increased apoptosis of circulating T cells in myelodysplastic syndromes (2007) Leuk Res, 31, pp. 1641-1648Nimer, S.D., MDS: a stem cell disorder - but what exactly is wrong with the primitive hematopoietic cells in this disease? (2008) Hematology Am Soc Hematol Educ Program, pp. 43-51Bynoe, A.G., Scott, C.S., Ford, P., Roberts, B.E., Decreased T helper cells in the myelodysplastic syndromes (1983) Br J Haematol, 54, pp. 97-102Hamblin, T.J., Immunological abnormalities in myelodysplastic syndromes (1996) Semin Hematol, 33, pp. 150-162Hamblin, T., Immunologic abnormalities in myelodysplastic syndromes (1992) Hematol Oncol Clin North Am, 6, pp. 571-586Amin, H.M., Jilani, I., Estey, E.H., Keating, M.J., Dey, A.L., Manshouri, T., Kantarjian, H.M., Albitar, M., Increased apoptosis in bone marrow B lymphocytes but not T lymphocytes in myelodysplastic syndrome (2003) Blood, 102, pp. 1866-1868Chan, A.C., Neeson, P., Leeansyah, E., Tainton, K., Quach, H., Prince, H.M., Godfrey, D.I., Berzins, S.P., Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients (2010) Leukemia, 24, pp. 592-600Hamada, K., Takahashi, I., Matsuoka, M., Saika, T., Mizobuchi, N., Yorimitsu, S., Takimoto, H., Apoptosis of peripheral leukocytes in patients with myelodysplastic syndromes (1998) Rinsho Ketsueki, 39, pp. 1079-1084Matsutani, T., Yoshioka, T., Tsuruta, Y., Shimamoto, T., Ohyashiki, J.H., Suzuki, R., Ohyashiki, K., Determination of T-cell receptors of clonal CD8-positive T-cells in myelodysplastic syndrome with erythroid hypoplasia (2003) Leuk Res, 27, pp. 305-312Epling-Burnette, P.K., Painter, J.S., Rollison, D.E., Ku, E., Vendron, D., Widen, R., Boulware, D., List, A.F., Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome (2007) Leukemia, 21, pp. 659-667Fozza, C., Contini, S., Galleu, A., Simula, M.P., Virdis, P., Bonfigli, S., Longinotti, M., Patients with myelodysplastic syndromes display several T-cell expansions, which are mostly polyclonal in the CD4(+) subset and oligoclonal in the CD8(+) subset (2009) Exp Hematol, 37, pp. 947-955Kook, H., Zeng, W., Guibin, C., Kirby, M., Young, N.S., Maciejewski, J.P., Increased cytotoxic T cells with effector phenotype in aplastic anemia and myelodysplasia (2001) Exp Hematol, 29, pp. 1270-1277Sloand, E.M., Melenhorst, J.J., Tucker, Z.C., Pfannes, L., Brenchley, J.M., Yong, A., Visconte, V., Young, N.S., T-cell immune responses to Wilms tumor 1 protein in myelodysplasia responsive to immunosuppressive therapy (2011) Blood, 117, pp. 2691-2699Maciejewski, J.P., Risitano, A., Sloand, E.M., Nunez, O., Young, N.S., Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia (2002) Blood, 99, pp. 3129-3135Sloand, E.M., Mainwaring, L., Fuhrer, M., Ramkissoon, S., Risitano, A.M., Keyvanafar, K., Lu, J., Young, N.S., Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome (2005) Blood, 106, pp. 841-851Chamuleau, M.E., Westers, T.M., van Dreunen, L., Groenland, J., Zevenbergen, A., Eeltink, C.M., Ossenkoppele, G.J., van de Loosdrecht, A.A., Immune mediated autologous cytotoxicity against hematopoietic precursor cells in patients with myelodysplastic syndrome (2009) Haematologica, 94, pp. 496-506Meers, S., Vandenberghe, P., Boogaerts, M., Verhoef, G., Delforge, M., The clinical significance of activated lymphocytes in patients with myelodysplastic syndromes: a single centre study of 131 patients (2008) Leuk Res, 32, pp. 1026-1035Symeonidis, A., Kourakli, A., Katevas, P., Perraki, M., Tiniakou, M., Matsouka, P., Georgoulias, V., Zoumbos, N., Immune function parameters at diagnosis in patients with myelodysplastic syndromes: correlation with the FAB classification and prognosis (1991) Eur J Haematol, 47, pp. 277-281Hamdi, W., Ogawara, H., Handa, H., Tsukamoto, N., Murakami, H., Clinical significance of Th1/Th2 ratio in patients with myelodysplastic syndrome (2009) Int J Lab Hematol, 31, pp. 630-638Hori, S., Nomura, T., Sakaguchi, S., Control of regulatory T cell development by the transcription factor Foxp3 (2003) Science, 299, pp. 1057-1061Hahn, B.H., Singh, R.P., La Cava, A., Ebling, F.M., Tolerogenic treatment of lupus mice with consensus peptide induces Foxp3-expressing, apoptosis-resistant, TGFbeta-secreting CD8+ T cell suppressors (2005) J Immunol, 175, pp. 7728-7737Wong, M., La Cava, A., Singh, R.P., Hahn, B.H., Blockade of programmed death-1 in young (New Zealand black x New Zealand white)F1 mice promotes the activity of suppressive CD8+ T cells that protect from lupus-like disease (2010) J Immunol, 185, pp. 6563-6571Frisullo, G., Nociti, V., Iorio, R., Plantone, D., Patanella, A.K., Tonali, P.A., Batocchi, A.P., CD8(+)Foxp3(+) T cells in peripheral blood of relapsing-remitting multiple sclerosis patients (2010) Hum Immunol, 71, pp. 437-441Tsai, Y.G., Yang, K.D., Niu, D.M., Chien, J.W., Lin, C.Y., TLR2 agonists enhance CD8+ Foxp3+ regulatory T cells and suppress Th2 immune responses during allergen immunotherapy (2010) J Immunol, 184, pp. 7229-7237Zhou, H., Wang, Z.D., Zhu, X., You, Y., Zou, P., CD8+ FOXP3+ T cells from renal transplant recipients in quiescence induce immunoglobulin-like transcripts-3 and -4 on dendritic cells from their respective donors (2007) Transplant Proc, 39, pp. 3065-3067Lerret, N.M., Houlihan, J.L., Kheradmand, T., Pothoven, K.L., Zhang, Z.J., Luo, X., Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells (2012) Am J Transplant, 12, pp. 2335-2347Fozza, C., Longu, F., Contini, S., Galleu, A., Virdis, P., Bonfigli, S., Murineddu, M., Longinotti, M., Patients with Early-Stage Myelodysplastic Syndromes Show Increased Frequency of CD4+CD25+CD127(low) Regulatory T Cells (2012) Acta Haematol, 128, pp. 178-182Kordasti, S.Y., Afzali, B., Lim, Z., Ingram, W., Hayden, J., Barber, L., Matthews, K., Mufti, G.J., IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome (2009) Br J Haematol, 145, pp. 64-72Alfinito, F., Sica, M., Luciano, L., Pepa, R.D., Palladino, C., Ferrara, I., Giani, U., Terrazzano, G., Immune dysregulation and dyserythropoiesis in the myelodysplastic syndromes (2009) Br J Haematol, 148, pp. 90-98Moore, K.W., de Waal Malefyt, R., Coffman, R.L., O'Garra, A., Interleukin-10 and the interleukin-10 receptor (2001) Annu Rev Immunol, 19, pp. 683-765Kang, S.S., Allen, P.M., Priming in the presence of IL-10 results in direct enhancement of CD8+ T cell primary responses and inhibition of secondary responses (2005) J Immunol, 174, pp. 5382-538