S. Sakaguchi, Naturally arising Foxp3-expressing CD251CD41 regulatory T cells in immunological tolerance to self and non-self, Nat Immunol, vol.6, pp.345-352, 2005.

T. R. Malek and I. Castro, Interleukin-2 receptor signaling: at the interface between tolerance and immunity, Immunity, vol.33, pp.153-165, 2010.

J. A. Bluestone, The yin and yang of interleukin-2-mediated immunotherapy, N Engl J Med, vol.365, pp.2129-2131, 2011.

O. Boyman and J. Sprent, The role of interleukin-2 during homeostasis and activation of the immune system, Nat Rev Immunol, vol.12, pp.180-190, 2012.

J. Matko, GPI-microdomains (membrane rafts) and signaling of the multichain interleukin-2 receptor in human lymphoma/leukemia T cell lines, Eur J Biochem, vol.269, pp.1199-1208, 2002.

X. Wang, M. Rickert, and K. C. Garcia, Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors, Science, vol.310, pp.1159-1163, 2005.

D. J. Stauber, E. W. Debler, P. A. Horton, K. A. Smith, and I. A. Wilson, Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor, Proc Natl Acad Sci U S A, vol.103, pp.2788-2793, 2006.

M. D. Marmor and M. Julius, Role for lipid rafts in regulating interleukin-2 receptor signaling, Blood, vol.98, pp.1489-1497, 2001.

P. E. Kovanen and W. J. Leonard, Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways, Immunol Rev, vol.202, pp.67-83, 2004.

B. H. Nelson, J. D. Lord, and P. D. Greenberg, Cytoplasmic domains of the interleukin-2 receptor beta and gamma chains mediate the signal for T-cell proliferation, Nature, vol.369, pp.333-336, 1994.

S. J. Bensinger, Distinct IL-2 receptor signaling pattern in CD41CD251 regulatory T cells, J Immunol, vol.172, pp.5287-5296, 2004.

M. A. Burchill, J. Yang, C. Vogtenhuber, B. R. Blazar, and M. Farrar, IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp31 regulatory T cells, J Immunol, vol.178, pp.280-290, 2007.

C. Nouze, L. Pasquet, and J. P. Van-meerwijk, In vitro expansion of alloantigenspecific regulatory T cells and their use in prevention of allograft rejection, Methods Mol Biol, vol.707, pp.187-196, 2011.

J. D. Fontenot, J. P. Rasmussen, M. A. Gavin, and A. Y. Rudensky, A function for interleukin 2 in Foxp3-expressing regulatory T cells, Nat Immunol, vol.6, pp.1142-1151, 2005.

R. Setoguchi, S. Hori, T. Takahashi, and S. Sakaguchi, Homeostatic maintenance of natural Foxp3(1) CD25(1) CD4(1) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization, J Exp Med, vol.201, pp.723-735, 2005.

D. Busse, Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments, Proc Natl Acad Sci U S A, vol.107, pp.3058-3063, 2010.

Y. Grinberg-bleyer, IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells, J Exp Med, vol.207, pp.1871-1878, 2011.

Q. Tang, Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction, Immunity, vol.28, pp.687-697, 2008.

J. Koreth, Interleukin-2 and regulatory T cells in graft-versus-host disease, N Engl J Med, vol.365, pp.2055-2066, 2011.

D. Saadoun, Regulatory T-cell responses to low-dose interleukin-2 in HCVinduced vasculitis, N Engl J Med, vol.365, pp.2067-2077, 2011.

A. Hartemann, Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial, Lancet Diabetes Endocrinol, vol.1, pp.295-305, 2013.

M. G. Kim, IL-2/anti-IL-2 complex attenuates renal ischemia-reperfusion injury through expansion of regulatory T cells, J Am Soc Nephrol, vol.24, pp.1529-1536, 2013.

S. Letourneau, IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25, Proc Natl Acad Sci U S A, vol.107, pp.2171-2176, 2010.

O. Boyman, M. Kovar, M. P. Rubinstein, C. D. Surh, and J. Sprent, Selective stimulation of T cell subsets with antibody-cytokine immune complexes, Science, vol.311, pp.1924-1927, 2006.

D. Kamimura and M. J. Bevan, Naive CD81 T cells differentiate into protective memory-like cells after IL-2 anti IL-2 complex treatment in vivo, J Exp Med, vol.204, pp.1803-1812, 2007.

K. E. Webster, In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression, J Exp Med, vol.206, pp.751-760, 2009.

C. Krieg, S. Letourneau, G. Pantaleo, and O. Boyman, Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells, Proc Natl Acad Sci U S A, vol.107, pp.11906-11911, 2010.

O. Boyman, Selectively expanding subsets of T cells in mice by injection of interleukin-2/antibody complexes: implications for transplantation tolerance, Transplant Proc, vol.44, pp.1032-1034, 2012.

M. O. Hottiger, P. O. Hassa, B. Luscher, H. Schuler, and F. Koch-nolte, Toward a unified nomenclature for mammalian ADP-ribosyltransferases, Trends Biochem Sci, vol.35, pp.208-219, 2010.

M. O. Hottiger, Progress in the function and regulation of ADP-Ribosylation, Sci Signal, vol.4, p.5, 2011.

L. Vitiello, S. Gorini, G. Rosano, and A. La-sala, Immunoregulation through extracellular nucleotides, Blood, vol.120, pp.511-518, 2012.

F. Haag, Extracellular NAD and ATP: Partners in immune cell modulation, Purinergic Signal, vol.3, pp.71-81, 2007.

F. Koch-nolte, S. Fischer, F. Haag, and M. Ziegler, Compartmentation of NAD1-dependent signalling, FEBS Lett, vol.585, pp.1651-1656, 2011.

S. Deaglio and S. C. Robson, Ectonucleotidases as regulators of purinergic signaling in thrombosis, inflammation, and immunity, Adv Pharmacol, vol.61, pp.301-332, 2011.

P. Bannas, Activity and specificity of toxin-related mouse T cell ecto-ADPribosyltransferase ART2.2 depends on its association with lipid rafts, Blood, vol.105, pp.3663-3670, 2005.

F. Aswad, H. Kawamura, and G. Dennert, High sensitivity of CD41CD251 regulatory T cells to extracellular metabolites nicotinamide adenine dinucleotide and ATP: a role for P2X7 receptors, J Immunol, vol.175, pp.3075-3083, 2005.

S. Hubert, Extracellular NAD1 shapes the Foxp31 regulatory T cell compartment through the ART2-P2X7 pathway, J Exp Med, vol.207, pp.2561-2568, 2010.

S. Adriouch, ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site, Faseb J, vol.22, pp.861-869, 2008.

G. Paone, ADP-ribosyltransferase-specific modification of human neutrophil peptide-1, J Biol Chem, vol.281, pp.17054-17060, 2006.

S. Laing, M. Unger, F. Koch-nolte, and F. Haag, ADP-ribosylation of arginine, Amino Acids, vol.41, pp.257-269, 2011.

, SCIENTIFIC REPORTS |, vol.5

F. Koch-nolte, Single domain antibodies from llama effectively and specifically block T cell ecto-ADP-ribosyltransferase ART2.2 in vivo, Faseb J, vol.21, pp.3490-3498, 2007.

K. Lahl, Selective depletion of Foxp31 regulatory T cells induces a scurfy-like disease, J Exp Med, vol.204, pp.57-63, 2007.

R. J. Robb, C. M. Rusk, and M. P. Neeper, Structure-function relationships for the interleukin 2 receptor: location of ligand and antibody binding sites on the Tac receptor chain by mutational analysis, Proc Natl Acad Sci U S A, vol.85, pp.5654-5658, 1988.

F. Scheuplein, NAD1 and ATP released from injured cells induce P2X7-dependent shedding of CD62L and externalization of phosphatidylserine by murine T cells, J Immunol, vol.182, pp.2898-2908, 2009.

D. T. Patton, M. D. Wilson, W. C. Rowan, D. R. Soond, and K. Okkenhaug, The PI3K p110delta regulates expression of CD38 on regulatory T cells, PLoS One, vol.6, p.17359, 2011.

C. Krebs, CD38 controls ADP-ribosyltransferase-2-catalyzed ADPribosylation of T cell surface proteins, J Immunol, vol.174, pp.3298-3305, 2005.

B. Rissiek, W. Danquah, F. Haag, and F. Koch-nolte, Advance: a new cell preparation strategy that greatly improves the yield of vital and functional Tregs and NKT cells, J Leukoc Biol, vol.95, pp.543-549, 2014.

P. Pandiyan, L. Zheng, S. Ishihara, J. Reed, and M. J. Lenardo, CD41CD251Foxp31 regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD41 T cells, Nat Immunol, vol.8, pp.1353-1362, 2007.

G. Churlaud, Sustained stimulation and expansion of Tregs by IL2 control autoimmunity without impairing immune responses to infection, vaccination and cancer, Clin Immunol, vol.151, pp.114-126, 2014.

S. Adriouch, NAD1 released during inflammation participates in T cell homeostasis by inducing ART2-mediated death of naive T cells in vivo, J Immunol, vol.179, pp.186-194, 2007.

T. Uchiyama, S. Broder, and T. A. Waldmann, A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (1) cells, J Immunol, vol.126, pp.1393-1397, 1981.

S. Kahl, Metalloprotease-mediated shedding of enzymatically active mouse ecto-ADP-ribosyltransferase ART2.2 upon T cell activation, J Immunol, vol.165, pp.4463-4469, 2000.

W. Ohlrogge, Generation and characterization of ecto-ADPribosyltransferase ART2.1/ART2.2-deficient mice, Mol Cell Biol, vol.22, pp.7535-7542, 2002.

J. M. Labasi, Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response, J Immunol, vol.168, pp.6436-6445, 2002.

F. Koch-nolte, A new monoclonal antibody detects a developmentally regulated mouse ecto ADP-ribosyltransferase on T cells: subset distribution, inbred strain variation, and modulation upon T cell activation, J Immunol, vol.163, pp.6014-6022, 1999.