M. J. Butte, M. E. Keir, T. B. Phamduy, A. H. Sharpe, and G. J. Freeman, Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses, Immunity, vol.27, pp.111-122, 2007.

H. Bour-jordan, J. H. Esensten, M. Martinez-llordella, C. Penaranda, and M. Stumpf, Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/B7 family, Immunol Rev, vol.241, pp.180-205, 2011.

T. Pentcheva-hoang, E. Corse, and J. P. Allison, Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections, Immunol Rev, vol.229, pp.67-87, 2009.

N. Poirier, G. Blancho, and B. Vanhove, CD28-specific immunomodulating antibodies: what can be learned from experimental models?, Am J Transplant, vol.12, pp.1682-1690, 2012.

D. M. Sansom, C. N. Manzotti, and Y. Zheng, What's the difference between CD80 and CD86?, Trends Immunol, vol.24, pp.314-319, 2003.

S. Kirchhoff, W. W. Muller, M. Li-weber, and P. H. Krammer, Up-regulation of cFLIPshort and reduction of activation-induced cell death in CD28-costimulated human T cells, Eur J Immunol, vol.30, pp.2765-2774, 2000.

G. J. Boonen, A. M. Van-dijk, L. F. Verdonck, R. A. Van-lier, and G. Rijksen, CD28 induces cell cycle progression by IL-2-independent down-regulation of p27kip1 expression in human peripheral T lymphocytes, Eur J Immunol, vol.29, pp.789-798, 1999.

P. Waterhouse, J. M. Penninger, E. Timms, A. Wakeham, and A. Shahinian, Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4, Science, vol.270, pp.985-988, 1995.

P. J. Blair, J. L. Riley, B. L. Levine, K. P. Lee, and N. Craighead, CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that inhibits interleukin-2 secretion but allows Bcl-X(L) induction, J Immunol, vol.160, pp.12-15, 1998.

T. L. Walunas, D. J. Lenschow, C. Y. Bakker, P. S. Linsley, and G. J. Freeman, CTLA-4 can function as a negative regulator of T cell activation, Immunity, vol.1, pp.405-413, 1994.

P. Scheipers and H. Reiser, Fas-independent death of activated CD4(+) T lymphocytes induced by CTLA-4 crosslinking, Proc Natl Acad Sci, vol.95, pp.10083-10088, 1998.

H. Schneider, J. Downey, A. Smith, B. H. Zinselmeyer, and C. Rush, Reversal of the TCR stop signal by CTLA-4, Science, vol.313, pp.1972-1975, 2006.

B. Wei, S. Da-rocha-dias, H. Wang, and C. E. Rudd, CTL-associated antigen-4 ligation induces rapid T cell polarization that depends on phosphatidylinositol 3-kinase, Vav-1, Cdc42, and myosin light chain kinase, J Immunol, vol.179, pp.400-408, 2007.

M. J. Butte, V. Pena-cruz, M. J. Kim, G. J. Freeman, and A. H. Sharpe, Interaction of human PD-L1 and B7-1, Mol Immunol, vol.45, pp.3567-3572, 2008.

B. T. Fife, K. E. Pauken, T. N. Eagar, T. Obu, and J. Wu, Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal, Nat Immunol, vol.10, pp.1185-1192, 2009.

B. Salomon, D. J. Lenschow, L. Rhee, N. Ashourian, and B. Singh, B7/ CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes, Immunity, vol.12, pp.431-440, 2000.

Y. Zheng, C. N. Manzotti, M. Liu, F. Burke, and K. I. Mead, CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells, J Immunol, vol.172, pp.2778-2784, 2004.

D. M. Sansom and L. S. Walker, The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology, Immunol Rev, vol.212, pp.131-148, 2006.

Y. M. Kerdiles, E. L. Stone, D. R. Beisner, M. A. Mcgargill, . Ch'en et al., Foxo transcription factors control regulatory T cell development and function, Immunity, vol.33, pp.890-904, 2010.

N. Ohkura and S. Sakaguchi, Foxo1 and Foxo3 help Foxp3, Immunity, vol.33, pp.835-837, 2010.

K. Wing, Y. Onishi, P. Prieto-martin, T. Yamaguchi, and M. Miyara, CTLA-4 control over Foxp3+ regulatory T cell function, Science, vol.322, pp.271-275, 2008.

M. J. Barnes, T. Griseri, A. M. Johnson, W. Young, and F. Powrie, CTLA-4 promotes Foxp3 induction and regulatory T cell accumulation in the intestinal lamina propria, Mucosal Immunol, 2012.

A. L. Mellor and D. H. Munn, IDO expression by dendritic cells: tolerance and tryptophan catabolism, Nat Rev Immunol, vol.4, pp.762-774, 2004.

O. S. Qureshi, Y. Zheng, K. Nakamura, K. Attridge, and C. Manzotti, Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4, Science, vol.332, pp.600-603, 2011.

Y. Onishi, Z. Fehervari, T. Yamaguchi, and S. Sakaguchi, Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation, Proc Natl Acad Sci U S A, vol.105, pp.10113-10118, 2008.

E. K. Page, W. A. Dar, and S. J. Knechtle, Biologics in organ transplantation, Transpl Int, vol.25, pp.707-719, 2012.

N. Poirier, C. Mary, N. Dilek, J. Hervouet, and D. Minault, Preclinical Efficacy and Immunological Safety of FR104, an Antagonist Anti-CD28 Monovalent Fab' Antibody, Am J Transplant, 2012.

S. Yao, Y. Zhu, G. Zhu, M. Augustine, and L. Zheng, B7-h2 is a costimulatory ligand for CD28 in human, Immunity, vol.34, pp.729-740, 2011.

N. Poirier, C. Mary, N. Dilek, J. Hervouet, and D. Minault, Preclinical efficacy and immunological safety of FR104, an antagonist anti-CD28 monovalent Fab' antibody, Am J Transplant, vol.12, pp.2630-2640, 2012.

C. Ibisch, X. Saulquin, G. Gallot, R. Vivien, and C. Ferrand, The T cell repertoire selected in vitro against EBV: diversity, specificity, and improved purification through early IL-2 receptor alpha-chain (CD25)-positive selection, J Immunol, vol.164, pp.4924-4932, 2000.

G. Gallot, S. Vollant, R. Vivien, B. Clemenceau, and C. Ferrand, Selection of Epstein-Barr virus specific cytotoxic T lymphocytes can be performed with B lymphoblastoid cell lines created in serum-free media, Clin Exp Immunol, vol.144, pp.158-168, 2006.
URL : https://hal.archives-ouvertes.fr/inserm-00473461

A. K. Abbas, C. Benoist, J. A. Bluestone, D. J. Campbell, and S. Ghosh, Regulatory T cells: recommendations to simplify the nomenclature, Nat Immunol, vol.14, pp.307-308, 2013.

C. Chauveau, S. Remy, P. J. Royer, M. Hill, and S. Tanguy-royer, Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression, Blood, vol.106, pp.1694-1702, 2005.

N. Poirier, A. M. Azimzadeh, T. Zhang, N. Dilek, and C. Mary, Inducing CTLA-4-dependent immune regulation by selective CD28 blockade promotes regulatory T cells in organ transplantation, Sci Transl Med, vol.2, pp.17-27, 2010.

C. Mary, F. Coulon, N. Poirier, N. Dilek, and B. Martinet, Antagonist properties of monoclonal antibodies targeting human CD28: Role of valency and the heavy-chain constant domain, MAbs, vol.5, 2012.

T. Takahashi, T. Tagami, S. Yamazaki, T. Uede, and J. Shimizu, Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4, J Exp Med, vol.192, pp.303-310, 2000.

A. Zanin-zhorov, Y. Ding, S. Kumari, M. Attur, and K. L. Hippen, Protein kinase C-theta mediates negative feedback on regulatory T cell function, Science, vol.328, pp.372-376, 2010.

B. Graf, T. Bushnell, and J. Miller, LFA-1-mediated T cell costimulation through increased localization of TCR/class II complexes to the central supramolecular activation cluster and exclusion of CD45 from the immunological synapse, J Immunol, vol.179, pp.1616-1624, 2007.

M. L. Dustin, M. W. Olszowy, A. D. Holdorf, J. Li, and S. Bromley, A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in Tcell contacts, Cell, vol.94, pp.667-677, 1998.

C. R. Monks, B. A. Freiberg, H. Kupfer, N. Sciaky, and A. Kupfer, Threedimensional segregation of supramolecular activation clusters in T cells, Nature, vol.395, pp.82-86, 1998.

S. P. Raychaudhuri, S. Kundu-raychaudhuri, K. Tamura, T. Masunaga, and K. Kubo, FR255734, a humanized, Fc-Silent, Anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model, J Invest Dermatol, vol.128, pp.1969-1976, 2008.

P. J. Perrin, C. H. June, J. H. Maldonado, R. B. Ratts, and M. K. Racke, Blockade of CD28 during in vitro activation of encephalitogenic T cells or after disease onset ameliorates experimental autoimmune encephalomyelitis, J Immunol, vol.163, pp.1704-1710, 1999.

P. B. Silver, K. S. Hathcock, C. C. Chan, B. Wiggert, and R. R. Caspi, Blockade of costimulation through B7/CD28 inhibits experimental autoimmune uveoretinitis, but does not induce long-term tolerance, J Immunol, vol.165, pp.5041-5047, 2000.

F. Haspot, C. Seveno, A. S. Dugast, F. Coulon, and K. Renaudin, Anti-CD28 Antibody-Induced Kidney Allograft Tolerance Related to Tryptophan Degradation and TCR Class II B7 Regulatory Cells, Am J Transplant, vol.5, pp.2339-2348, 2005.

T. Zhang, S. Fresnay, E. Welty, N. Sangrampurkar, and E. Rybak, Selective CD28 blockade attenuates acute and chronic rejection of murine cardiac allografts in a CTLA-4-dependent manner, Am J Transplant, vol.11, pp.1599-1609, 2011.

T. M. Holling, E. Schooten, and P. J. Van-den-elsen, Function and regulation of MHC class II molecules in T-lymphocytes: of mice and men, Hum Immunol, vol.65, pp.282-290, 2004.

N. Poirier, G. Blancho, and B. Vanhove, Alternatives to calcineurin inhibition in renal transplantation: belatacept, the first co-stimulation blocker, Immunotherapy, vol.2, pp.625-636, 2010.

T. Tomiyama, Y. Ueda, T. Katakai, N. Kondo, and K. Okazaki, Antigenspecific suppression and immunological synapse formation by regulatory T cells require the mst1 kinase, PLoS One, vol.8, p.73874, 2013.

Y. Lu, H. Schneider, and C. E. Rudd, Murine regulatory T cells differ from conventional T cells in resisting the CTLA-4 reversal of TCR stop-signal, Blood, vol.120, pp.4560-4570, 2012.

H. Schneider, E. Valk, S. Da-rocha-dias, B. Wei, and C. E. Rudd, CTLA-4 upregulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function, Proc Natl Acad Sci U S A, vol.102, pp.12861-12866, 2005.

T. J. Dillon, K. D. Carey, S. A. Wetzel, D. C. Parker, and P. J. Stork, Regulation of the small GTPase Rap1 and extracellular signal-regulated kinases by the costimulatory molecule CTLA-4, Mol Cell Biol, vol.25, pp.4117-4128, 2005.

A. Mor, M. L. Dustin, and M. R. Philips, Small GTPases and LFA-1 reciprocally modulate adhesion and signaling, Immunol Rev, vol.218, pp.114-125, 2007.

Y. Chen, S. Shen, B. K. Gorentla, J. Gao, and X. P. Zhong, Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression, J Immunol, vol.188, pp.1698-1707, 2012.

T. Gogishvili, F. Luhder, S. Goebbels, S. Beer-hammer, and K. Pfeffer, Cell-intrinsic and -extrinsic control of Treg-cell homeostasis and function revealed by induced CD28 deletion, Eur J Immunol, vol.43, pp.188-193, 2013.

Q. Tang, K. J. Henriksen, E. K. Boden, A. J. Tooley, and J. Ye, Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells, J Immunol, vol.171, pp.3348-3352, 2003.

H. Chavez, S. Beaudreuil, K. Abbed, Y. Taoufic, and F. Kriaa, Absence of CD4CD25 regulatory T cell expansion in renal transplanted patients treated in vivo with Belatacept mediated CD28-CD80/86 blockade, Transpl Immunol, vol.17, pp.243-248, 2007.

C. Alvarez-quiroga, C. Abud-mendoza, L. Doniz-padilla, A. Juarez-reyes, and A. Monsivais-urenda, CTLA-4-Ig therapy diminishes the frequency but enhances the function of Treg cells in patients with rheumatoid arthritis, J Clin Immunol, vol.31, pp.588-595, 2011.

F. W. Vondran, K. Timrott, S. Kollrich, J. Klempnauer, and R. Schwinzer, Decreased frequency of peripheral CD4(+) CD161(+) Th(17) -precursor cells in kidney transplant recipients on long-term therapy with Belatacept, Transpl Int, vol.25, pp.455-463, 2012.