nTreg Cell-Mediated Suppression of Dendritic Cell Activation. Cellular Immunology, 265, 91-96.

[35]   Tsang, J.Y., Tanriver, Y., Jiang, S., et al. (2009) Indefinite Mouse Heart Allograft Survival in Recipient Treated with CD4+CD25+ Regulatory T Cells with Indirect Allospecificity and Short Term Immunosuppression. Transplant Immunology, 21, 203-209.

[36]   Golshayan, D., Jiang, S., Tsang, J., Garin, M.I., Mottet, C. and Lechler, R.I. (2007) In Vitro-Expanded Donor Alloantigen-Specific CD4+CD25+ Regulatory T Cells Promote Experimental Transplantation Tolerance. Blood, 109, 827-835.

[37]   Joffre, O., Santolaria, T., Calise, D., et al. (2008) Prevention of Acute and Chronic Allograft Rejection with CD4+ CD25+Foxp3+ Regulatory T Lymphocytes. Nature Medicine, 14, 88-92.

[38]   Cao, T., Soto, A., Zhou, W., et al. (2009) Ex Vivo Expanded Human CD4+CD25+Foxp3+ Regulatory T Cells Prevent Lethal Xenogenic Graft versus Host Disease (GVHD). Cellular Immunology, 258, 65-71.

[39]   Shalev, I., Schmelzle, M., Robson, S.C. and Levy, G. (2011) Making Sense of Regulatory T Cell Suppressive Function. Seminars in Immunology, 23, 282-292.

[40]   Nadig, S.N., Wieckiewicz, J., Wu, D.C., et al. (2010) In Vivo Prevention of Transplant Arteriosclerosis by ex Vivo-Expanded Human Regulatory T Cells. Nature Medicine, 16, 809-813.

[41]   Issa, F., Hester, J., Goto, R., Nadig, S.N., Goodacre, T.E. and Wood, K. (2010) Ex Vivo-Expanded Human Regulatory T Cells Prevent the Rejection of Skin Allografts in a Humanized Mouse Model. Transplantation, 90, 1321-1327.

[42]   Tran, D.Q., Andersson, J., Hardwick, D., Bebris, L., Illei, G.G. and Shevach, E.M. (2009) Selective Expression of Latency-Associated Peptide (LAP) and IL-1 Receptor Type I/II (CD121a/CD121b) on Activated Human FOXP3+ Regulatory T Cells Allows for Their Purification from Expansion Cultures. Blood, 113, 5125-5133.

[43]   Ukena, S.N., Hopting, M., Velaga, S., et al. (2011) Isolation Strategies of Regulatory T Cells for Clinical Trials: Phenotype, Function, Stability, and Expansion Capacity. Experimental Hematology, 39, 1152-1160.

[44]   Marek, N., Bieniaszewska, M., Krzystyniak, A., et al. (2011) The Time Is Crucial for ex Vivo Expansion of T Regulatory Cells for Therapy. Cell Transplantation, 20, 1747-1758.

[45]   Tresoldi, E., Dell’Albani, I., Stabilini, A., et al. (2011) Stability of Human Rapamycin-Expanded CD4+CD25+ T Regu- latory Cells. Haematologica, 96, 1357-1365.

[46]   Gurkan, S., Luan, Y., Dhillon, N., et al. (2010) Immune Reconstitution Following Rabbit Antithymocyte Globulin. American Journal of Transplantation, 10, 2132-2141.

[47]   Sojka, D.K., Huang, Y.-H. and Fowell, D.J. (2008) Mechanisms of Regulatory T-Cell Suppression—A Diverse Arsenal for a Moving Target. Immunology, 124, 13-22.

[48]   Lim, H.W., Hillsamer, P., Banham, A.H. and Kim, C.H. (2005) Cutting Edge: Direct Suppression of B Cells by CD4+ CD25+ Regulatory T Cells. The Journal of Immunology, 175, 4180-4183.

[49]   Fan, Z., Spencer, J.A., Lu, Y., et al. (2010) In Vivo Tracking of “Color-Coded” Effector, Natural and Induced Regulatory T Cells in the Allograft Response. Nature Medicine, 16, 718-722.

[50]   Tsang, J.Y., Ratnasothy, K., Li, D., et al. (2011) The Potency of Allospecific Tregs Cells Appears to Correlate with T Cell Receptor Functional Avidity. American Journal of Transplantation, 11, 1610-1620.

[51]   Feng, G., Nadig, S.N., Backdahl, L., et al. (2011) Functional Regulatory T Cells Produced by Inhibiting Cyclic Nucleotide Phosphodiesterase Type 3 Prevent Allograft Rejection. Science Translational Medicine, 3, 83ra40.

[52]   Ding, Y., Xu, J. and Bromberg, J.S. (2012) Regulatory T Cell Migration during an Immune Response. Trends in Immunology, 33, 174-180.

[53]   Duhen, T., Duhen, R., Lanzavecchia, A., Sallusto, F. and Campbell, D.J. (2012) Functionally Distinct Subsets of Human FOXP3+ Treg Cells That Phenotypically Mirror Effector Th Cells. Blood, 119, 4430-4440.

[54]   Sagoo, P., Perucha, E., Sawitzki, B., et al. (2010) Development of a Cross-Platform Biomarker Signature to Detect Renal Transplant Tolerance in Humans. Journal of Clinical Investigation, 120, 1848-1861.

[55]   Di Ianni, M., Falzetti, F., Carotti, A., et al. (2011) Tregs Prevent GVHD and Promote Immune Reconstitution in HLA-Haploidentical Transplantation. Blood, 117, 3921-3928.

[56]   Kimura, A. and Kishimoto, T. (2010) IL-6: Regulator of Treg/Th17 Balance. European Journal of Immunology, 40, 1830-1835.

[57]   Fujimoto, M., Nakano, M., Terabe, F., et al. (2011) The Influence of Excessive IL-6 Production in Vivo on the Development and Function of Foxp3+ Regulatory T Cells. The Journal of Immunology, 186, 32-40.

[58]   Kim, J., Sonawane, S., Lee, M.K., et al. (2010) Blockade of GITR-GITRL Interaction Maintains Regulatory T Cell Function to Prolong Allograft Survival. European Journal of Immunology, 40, 1369-1374.

[59]   Quigley, M.F. (2010) Convergent Recombination Shapes the Clonotypic Landscape of the Naive T-Cell Repertoire. Proceedings of the National Academy of Sciences of the United States of America, 107, 19414-19419.

[60]   Thomas, P.G., Handel, A., Doherty, P.C., et al. (2013) Ecological Analysis of Antigen-Specific CTL Repertoires Defines the Relationship between Naive and Immune T-Cell Populations. Proceedings of the National Academy of Sciences of the United States of America, 110, 1839-1844.

[61]   Guillonneau, C., Picarda, E. and Anegon, I. (2010) CD8+ Regulatory T Cells in Solid Organ Transplantation. Current Opinion in Organ Transplantation, 15, 751-756.

[62]   Li, X.L., et al. (2010) Mechanism and Localization of CD8 Regulatory T Cells in a Heart Transplant Model of Tolerance. The Journal of Immunology, 185, 823-833.

[63]   Picarda, E., Anegon, I. and Guillonneau, C. (2011) T-Cell Receptor Specificity of CD8+ Tregs in Allotransplantation. Immunotherapy, 3, 35-37.

[64]   Sagoo, P., Ali, N., Garg, G., et al. (2011) Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Polyclonal Regulatory T Cells. Science Translational Medicine, 3, 83-92.

[65]   Pasquet, L., Joffre, O., Santolaria, T., et al. (2011) Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells. Frontiers in Immunology, 2, 80.

[66]   Ohkura, N. and Sakaguchi, S. (2010) Regulatory T Cells: Roles of T Cell Receptor for Their Development and Function. Seminars in Immunopathology, 32, 95-106.

[67]   Fohse, L. (2011) High TCR Diversity Ensures Optimal Function and Homeostasis of Foxp3+ Regulatory T Cells. European Journal of Immunology, 41, 3101-3113.

[68]   Wood, K.J., Bushell, A. and Hester, J. (2012) Regulatory Immune Cells in Transplantation. Nature Reviews Immuno- logy, 12, 417-430.

[69]   Liu, Y.C. (2012) The Energetic Basis Underpinning T-Cell Receptor Recognition of a Super-Bulged Peptide Bound to a Major Histo-compatibility Complex Class I Molecule. The Journal of Biological Chemistry, 287, 12267-12276.

[70]   Ekeruche-Makinde, J. (2013) Peptide Length Determines the Outcome of TCR/Peptide-MHCI Engagement. Blood, 121, 1112-1123.

[71]   Leavenworth, J.W., Tang, X., Kim, H.J., et al. (2013) Amelioration of Arthritis through Mobilization of Peptide-Specific CD8+ Regulatory T Cells. Journal of Clinical Investigation, 123, 1382-1389.

[72]   Muller, Y.D., Seebach, J.D., Bühler, L.H., et al. (2011) Trans-plantation Tolerance: Clinical Potential of Regulatory T Cells. Self/Nonself, 2, 26-34.

[73]   Pilat, N., Farkas, A.M., et al. (2014) T-Regulatory Cell Treatment Prevents Chronic Rejection of Heart Allografts in a Murine Mixed Chimerism Model. The Journal of Heart and Lung Transplantation, 33, 429-437.

[74]   Darrasse-Jèze, G. and Podsypanina, K. (2013) How Numbers, Nature, and Immune Status of Foxp3+ Regulatory T- Cells Shape the Early Immunological Events in Tumor Development. Frontiers in Immunology, 4, 292.

[75]   Hollenbeak, C.S., Todd, M.M., Billingsley, E.M., et al. (2005) Increased Incidence of Melanoma in Renal Transplantation Recipients. Cancer, 104, 1962-1710.

[76]   Zhang, L., Conejo-Garcia, J.R., Katsaros, D., et al. (2003) Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer. The New England Journal of Medicine, 348, 203-213.

[77]   Liyanage, U.K., Moore, T.T., Joo, H.G., et al. (2002) Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma. The Journal of Immunology, 169, 2756-2761.

[78]   deLeeuw, R.J., Kost, S.E., Kakal, J.A., et al. (2012) The Prognostic Value of FoxP3+ Tumor-Infiltrating Lymphocytes in Cancer: A Critical Review of the Literature. Clinical Cancer Research, 102, 345-352.

[79]   Martin, F., Ladoire, S., Mignot, G., et al. (2010) Human FOXP3 and Cancer. Oncogene, 29, 4121-4129.

[80]   Tanchot, C., Terme, M., Pere, H., et al. (2012) Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion in Situ and Clinical Significance. Cancer Microenvironment, 6, 147-157.

[81]   Ladoire, S., Martin, F. and Ghiringhelli, F. (2011) Prognostic Role of FOXP3+ Regulatory T Cells Infiltrating Human Carcinomas: The Paradox of Colorectal Cancer. Cancer Immunology, Immunotherapy, 60, 909-918.

[82]   Ghoreschi, K., Laurence, A., Yang, X.P., et al. (2010) Generation of Pathogenic TH17 Cells in the Absence of TGF-Beta Signalling. Nature, 467, 967-971.

[83]   Baratelli, F., Lee, J.M., Hazra, S., et al. (2010) PGE(2) Contributes to TGF-Beta Induced T Regulatory Cell Function in Human Non-Small Cell Lung Cancer. American Journal of Translational Research, 2, 356-367.

[84]   Willimsky, G. and Blankenstein, T. (2005) Sporadic Immunogenic Tumours Avoid Destruction by Inducing T-Cell Tolerance. Nature, 437, 141-146.

[85]   Savage, P.A., Malchow, S. and Leventhal, D.S. (2013) Basic Principles of Tumor-Associated Regulatory T Cell Bio- logy. Trends in Immunology, 34, 33-40.

[86]   Fontenot, J.D., Rasmussen, J.P., Williams, L.M., et al. (2005) Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3. Immunity, 22, 329-341.

[87]   Getnet, D., Grosso, J.F., Goldberg, M.V., et al. (2010) A Role for the Transcription Factor Helios in Human CD4+ CD25+ Regulatory T Cells. Molecular Immunology, 47, 1595-1600.

[88]   Thornton, A.M., Korty, P.E., Tran, D.Q., et al. (2010) Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3+ T Regulatory Cells. The Journal of Immunology, 184, 3433-3441.

[89]   Malchow, S., Leventhal, D.S., Nishi, S., et al. (2013) Aire-Dependent Thymic Development of Tumor-Associated Regulatory T Cells. Science, 339, 1219-1224.

[90]   Paiva, R.S., Lino, A.C., Bergman, M.L., et al. (2013) Recent Thymic Emigrants Are the Preferential Precursors of Regulatory T Cells Differentiated in the Periphery. Proceedings of the National Academy of Sciences of the United States of America, 110, 6494-6499.

[91]   Vence, L., Palucka, A.K., Fay, J.W., et al. (2007) Circulating Tumor Antigen-Specific Regulatory T Cells in Patients with Metastatic Melanoma. Proceedings of the National Academy of Sciences of the United States of America, 104, 20884-20889.

[92]   Szajnik, M., Czystowska, M., Szczepanski, M.J., et al. (2010) Tumor-Derived Microvesicles Induce, Expand and Up-Regulate Biological Activities of Human Regulatory T Cells (Treg). PLoS ONE, 5, e11469.

[93]   Wehrens, E.J., Mijnheer, G., Duurland, C.L., et al. (2011) Functional Human Regulatory T Cells Fail to Control Autoimmune Inflammation Due to PKB/c-akt Hyperactivation in Effector Cells. Blood, 118, 3538-3548.

[94]   Quintana, F.J., Iglesias, A.H., Farez, M.F., et al. (2010) Adaptive Autoimmunity and Foxp3-Based Immunoregulation in Zebrafish. PLoS ONE, 5, e9478.

[95]   Samstein, R.M., Josefowicz, S.Z., Arvey, A., et al. (2012) Extrathymic Generation of Regulatory T Cells in Placental Mammals Mitigates Maternal-Fetal Conflict. Cell, 150, 29-38.

[96]   Maury, S., Lemoine, F.M., Hicheri, Y., et al. (2010) CD4+CD25+ Regulatory T Cell Depletion Improves the Graft- versus-Tumor Effect of Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation. Science Translational Medicine, 2, 41-52.

[97]   Dons, E.M., Raimondi, G., Cooper, D.K.C., et al. (2010) Non-Human Primate Regulatory T Cells: Current Biology and Implications for Transplantation. Transplantation, 90, 811-816.

[98]   Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674.

[99]   Koebel, C.M., Vermi, W., Swann, J.B., et al. (2007) Adaptive Immunity Maintains Occult Cancer in an Equilibrium State. Nature, 450, 903-924.

[100]   Menetrier-Caux, C., Curiel, T., Faget, J., et al. (2012) Targeting Regulatory T Cells. Targeted Oncology, 7, 15-28.

[101]   Yamaguchi, T., Wing, J.B. and Sakaguchi, S. (2011) Two Modes of Immune Suppression by Foxp3+ Regulatory T Cells under Inflammatory or Non-Inflammatory Conditions. Seminars in Immunology, 23, 424-430.

[102]   Miyao, T., Floess, S., Setoguchi, R., et al. (2012) Plasticity of Foxp3(+) T Cells Reflects Promiscuous Foxp3 Expression in Conventional T Cells but Not Reprogramming of Regulatory T Cells. Immunity, 36, 262-275.

[103]   Elkord, E., Sharma, S., Burt, D.J. and Hawkins, R.E. (2011) Expanded Subpopulation of FoxP3+ T Regulatory Cells in Renal Cell Carcinoma Co-Express Helios, Indicating They Could Be Derived from Natural but Not Induced Tregs. Clinical Immunology, 140, 218-222.