AGENTE ESPUMANTE

immunotherapeutic strategies for transplantation purposes in preclinical models. Recently, the first clinical trials using infusion of ex vivo selected nTreg and ex vivo generated iTreg have been started in stem cell transplantation recipients. These studies will provide crucial information about the safety and clinical potential of Treg infusion immunotherapy. However, issues regarding the identification of stable Treg, and in vivo behavior of these cells upon infusion remain to be elucidated. Also, technical limitations regarding GMP Treg isolation still challenge successful application of Treg based therapies.

REfERENCEs

1. Meier-Kriesche,H.U., Schold,J.D., and Kaplan,B., long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies? am.J.transplant. 2004. 4: 1289-1295.

2. Alyea,E.P., Modulating graft-versus-host disease to enhance the graft-versus-leukemia effect. Best.Pract.Res.clin.Haematol. 2008. 21: 239-250.

3. Kolb,H.J., Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008. 112: 4371-4383.

4. Pacholczyk,R. and Kern,J., The T-cell receptor repertoire of regulatory T cells. Immunology. 2008. 125: 450-458.

5. Cohen,J.l., Trenado,A., Vasey,D., Klatzmann,D., and Salomon,B.l., CD4(+)CD25(+) immunoregulatory T Cells: new therapeutics for graft-versus-host disease. J.exp.Med. 2002. 196: 401-406.

6. Hoffmann,P., Ermann,J., Edinger,M., Fathman,C.G., and Strober,S., Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J.exp.Med. 2002. 196: 389-399.

7. Taylor,P.A., lees,C.J., and Blazar,B.R., The infusion of ex vivo activated and expanded CD4(+) CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002. 99: 3493-3499.

8. Edinger,M., Hoffmann,P., Ermann,J., Drago,K., Fathman,C.G., Strober,S., and Negrin,R.S., CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus- host disease after bone marrow transplantation. nat.med. 2003. 9: 1144-1150.

9. Jones,S.C., Murphy,G.F., and Korngold,R., Post-hematopoietic cell transplantation control of graft- versus-host disease by donor CD425 T cells to allow an effective graft-versus-leukemia response. Biol.Blood Marrow transplant. 2003. 9: 243-256.

10. Trenado,A., Charlotte,F., Fisson,S., yagello,M., Klatzmann,D., Salomon,B.l., and Cohen,J.l., Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia. J.clin.Invest. 2003. 112: 1688- 1696.

11. Joffre,O., Gorsse,N., Romagnoli,P., Hudrisier,D., and van Meerwijk,J.P., Induction of antigen- specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes. Blood. 2004. 103: 4216-4221.

12. Hanash,A.M. and levy,R.B., Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC-mismatched hematopoietic cell transplantation. Blood. 2005. 105: 1828-1836. 13. Nguyen,V.H., Zeiser,R., Dasilva,D.l., Chang,D.S., Beilhack,A., Contag,C.H., and Negrin,R.S., In vivo

dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft- versus-host disease following allogeneic transplantation. Blood. 2007. 109: 2649-2656.

14. Kingsley,C.I., Karim,M., Bushell,A.R., and Wood,K.J., CD25+CD4+ regulatory T cells prevent graft rejection: CTlA-4- and Il-10-dependent immunoregulation of alloresponses. J.Immunol. 2002.

2

168: 1080-1086.

15. Nishimura,E., Sakihama,T., Setoguchi,R., Tanaka,K., and Sakaguchi,S., Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells. int.immunol. 2004. 16: 1189-1201.

16. Golshayan,D., Jiang,S., Tsang,J., Garin,M.I., Mottet,C., and lechler,R.I., In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance. Blood. 2007. 109: 827-835.

17. Chai,J.G., Coe,D., Chen,D., Simpson,E., Dyson,J., and Scott,D., In vitro expansion improves in vivo regulation by CD4+CD25+ regulatory T cells. J.Immunol. 2008. 180: 858-869.

18. Joffre,O., Santolaria,T., Calise,D., Al,S.T., Hudrisier,D., Romagnoli,P., and van Meerwijk,J.P., Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes. nat.med. 2008. 14: 88-92.

19. yuen-Shan,T.J., Tanriver,y., Jiang,S., leung,E., Ratnasothy,K., lombardi,G., and lechler,R., Indefinite mouse heart allograft survival in recipient treated with CD4(+)CD25(+) regulatory T cells with indirect allospecificity and short term immunosuppression. transpl.immunol. 2009. 21:203-209. 20. louis,S., Braudeau,C., Giral,M., Dupont,A., Moizant,F., Robillard,N., Moreau,A., Soulillou,J.P., and

Brouard,S., Contrasting CD25hiCD4+T cells/FOXP3 patterns in chronic rejection and operational drug-free tolerance. transplantation. 2006. 81: 398-407.

21. Wolf,D., Wolf,A.M., Fong,D., Rumpold,H., Strasak,A., Clausen,J., and Nachbaur,D., Regulatory T-cells in the graft and the risk of acute graft-versus-host disease after allogeneic stem cell transplantation. transplantation. 2007. 83: 1107-1113.

22. Zhai,Z., Sun,Z., li,Q., Zhang,A., liu,H., Xu,J., Xu,X., Geng,l., Harris,D., Hu,S., and Wang,y., Correlation of the CD4+CD25high T-regulatory cells in recipients and their corresponding donors to acute GVHD. transpl.int. 2007. 20: 440-446.

23. Salama,A.D., Najafian,N., Clarkson,M.R., Harmon,W.E., and Sayegh,M.H., Regulatory CD25+ T cells in human kidney transplant recipients. J.am.soc.Nephrol. 2003. 14: 1643-1651.

24. Meloni,F., Vitulo,P., Bianco,A.M., Paschetto,E., Morosini,M., Cascina,A., Mazzucchelli,I., Ciardelli,l., Oggionni,T., Fietta,A.M., Pozzi,E., and Vigano,M., Regulatory CD4+CD25+ T cells in the peripheral blood of lung transplant recipients: correlation with transplant outcome. transplantation. 2004. 77: 762-766.

25. Demirkiran,A., Kok,A., Kwekkeboom,J., Kusters,J.G., Metselaar,H.J., Tilanus,H.W., and van der laan,l.J., low circulating regulatory T-cell levels after acute rejection in liver transplantation. Liver transpl. 2006. 12: 277-284.

26. Bestard,O., Cruzado,J.M., Rama,I., Torras,J., Goma,M., Seron,D., Moreso,F., Gil-Vernet,S., and Grinyo,J.M., Presence of FoxP3+ regulatory T Cells predicts outcome of subclinical rejection of renal allografts. J.am.soc.Nephrol. 2008. 19: 2020-2026.

27. Shevach,E.M., From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity. 2006. 25: 195-201.

28. Baecher-Allan,C., Brown,J.A., Freeman,G.J., and Hafler,D.A., CD4+CD25high regulatory cells in human peripheral blood. J.Immunol. 2001. 167: 1245-1253.

29. Albert,M.H., liu,y., Anasetti,C., and yu,X.Z., Antigen-dependent suppression of alloresponses by Foxp3-induced regulatory T cells in transplantation. eur.J.Immunol. 2005. 35: 2598-2607.

30. Karakhanova,S., Munder,M., Schneider,M., Bonyhadi,M., Ho,A.D., and Goerner,M., Highly efficient expansion of human CD4+CD25+ regulatory T cells for cellular immunotherapy in patients with graft-versus-host disease. J.Immunother. 2006. 29: 336-349.

31. Merlo,A., Tagliabue,E., Menard,S., and Balsari,A., Matured human monocyte-derived dendritic cells (MoDCs) induce expansion of CD4(+)CD25(+)FOXP3(+) T cells lacking regulatory properties. Immunol.lett. 2008. 117: 106-113.

32. Huehn,J., Polansky,J.K., and Hamann,A., Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? nat.rev.immunol. 2009. 9: 83-89.

33. Baron,U., Floess,S., Wieczorek,G., Baumann,K., Grutzkau,A., Dong,J., Thiel,A., Boeld,T.J., Hoffmann,P., Edinger,M., Turbachova,I., Hamann,A., Olek,S., and Huehn,J., DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. eur.J.Immunol. 2007. 37: 2378-2389.

demethylation reveals the committed Treg population in humans. Plos oNe. 2008. 3: e1612. 35. Nagar,M., Vernitsky,H., Cohen,y., Dominissini,D., Berkun,y., Rechavi,G., Amariglio,N., and

Goldstein,I., Epigenetic inheritance of DNA methylation limits activation-induced expression of FOXP3 in conventional human CD25-CD4+ T cells. int.immunol. 2008. 20: 1041-1055.

36. Polansky,J.K., Kretschmer,K., Freyer,J., Floess,S., Garbe,A., Baron,U., Olek,S., Hamann,A., von,B.H., and Huehn,J., DNA methylation controls Foxp3 gene expression. eur.J.Immunol. 2008. 38: 1654- 1663.

37. liu,W., Putnam,A.l., Xu-yu,Z., Szot,G.l., lee,M.R., Zhu,S., Gottlieb,P.A., Kapranov,P., Gingeras,T.R., de St Groth,B.F., Clayberger,C., Soper,D.M., Ziegler,S.F., and Bluestone,J.A., CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J.exp.Med. 2006. 203: 1701-1711.

38. Seddiki,N., Santner-Nanan,B., Martinson,J., Zaunders,J., Sasson,S., landay,A., Solomon,M., Selby,W., Alexander,S.I., Nanan,R., Kelleher,A., and de St Groth,B.F., Expression of interleukin (Il)- 2 and Il-7 receptors discriminates between human regulatory and activated T cells. J.exp.Med. 2006. 203: 1693-1700.

39. Aerts,N.E., Dombrecht,E.J., Ebo,D.G., Bridts,C.H., Stevens,W.J., and De Clerck,l.S., Activated T cells complicate the identification of regulatory T cells in rheumatoid arthritis. cell Immunol. 2008. 251: 109-115.

40. Kleinewietfeld,M., Starke,M., Di,M.D., Borsellino,G., Battistini,l., Rotzschke,O., and Falk,K., CD49d provides access to “untouched” human Foxp3+ Treg free of contaminating effector cells. Blood. 2009. 113: 827-836.

41. Raimondi,G., Shufesky,W.J., Tokita,D., Morelli,A.E., and Thomson,A.W., Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells. J.Immunol. 2006. 176: 2808-2816.

42. Shimizu,J., yamazaki,S., Takahashi,T., Ishida,y., and Sakaguchi,S., Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. nat.immunol. 2002. 3: 135- 142.

43. McHugh,R.S., Whitters,M.J., Piccirillo,C.A., young,D.A., Shevach,E.M., Collins,M., and Byrne,M.C., CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity. 2002. 16: 311-323.

44. Dieckmann,D., Plottner,H., Berchtold,S., Berger,T., and Schuler,G., Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J.exp. med. 2001. 193: 1303-1310.

45. Nakamura,K., Kitani,A., and Strober,W., Cell contact-dependent immunosuppression by CD4(+) CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J.exp.Med. 2001. 194: 629-644.

46. Sarris,M., Andersen,K.G., Randow,F., Mayr,l., and Betz,A.G., Neuropilin-1 expression on regulatory T cells enhances their interactions with dendritic cells during antigen recognition. Immunity. 2008. 28: 402-413.

47. yamaguchi,T., Hirota,K., Nagahama,K., Ohkawa,K., Takahashi,T., Nomura,T., and Sakaguchi,S., Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity. 2007. 27: 145-159.

48. Borsellino,G., Kleinewietfeld,M., Di,M.D., Sternjak,A., Diamantini,A., Giometto,R., Hopner,S., Centonze,D., Bernardi,G., Dell’Acqua,M.l., Rossini,P.M., Battistini,l., Rotzschke,O., and Falk,K., Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007. 110: 1225-1232.

49. Deaglio,S., Dwyer,K.M., Gao,W., Friedman,D., Usheva,A., Erat,A., Chen,J.F., Enjyoji,K., linden,J., Oukka,M., Kuchroo,V.K., Strom,T.B., and Robson,S.C., Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J.exp.Med. 2007. 204: 1257- 1265.

50. Valmori,D., Merlo,A., Souleimanian,N.E., Hesdorffer,C.S., and Ayyoub,M., A peripheral circulating compartment of natural naive CD4 Tregs. J.clin.Invest. 2005. 115: 1953-1962.

51. Seddiki,N., Santner-Nanan,B., Tangye,S.G., Alexander,S.I., Solomon,M., lee,S., Nanan,R., and de Saint Groth,B.F., Persistence of naive CD45RA+ regulatory T cells in adult life. Blood. 2006. 107: 2830-2838.

2

52. Menning,A., Hopken,U.E., Siegmund,K., lipp,M., Hamann,A., and Huehn,J., Distinctive role

of CCR7 in migration and functional activity of naive- and effector/memory-like Treg subsets. eur.J.Immunol. 2007. 37: 1575-1583.

53. Tosello,V., Odunsi,K., Souleimanian,N.E., lele,S., Shrikant,P., Old,l.J., Valmori,D., and Ayyoub,M., Differential expression of CCR7 defines two distinct subsets of human memory CD4+CD25+ Tregs. clin.Immunol. 2008. 126: 291-302.

54. Koenen,H.J., Fasse,E., and Joosten,I., CD27/CFSE-based ex vivo selection of highly suppressive alloantigen-specific human regulatory T cells. J.Immunol. 2005. 174: 7573-7583.

55. Ruprecht,C.R., Gattorno,M., Ferlito,F., Gregorio,A., Martini,A., lanzavecchia,A., and Sallusto,F., Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia. J.exp. med. 2005. 201: 1793-1803.

56. Duggleby,R.C., Shaw,T.N., Jarvis,l.B., Kaur,G., and Gaston,J.S., CD27 expression discriminates between regulatory and non-regulatory cells after expansion of human peripheral blood CD4+ CD25+ cells. Immunology. 2007. 121: 129-139.

57. Baecher-Allan,C., Wolf,E., and Hafler,D.A., MHC class II expression identifies functionally distinct human regulatory T cells. J.Immunol. 2006. 176: 4622-4631.

58. Walker,l.S., Regulatory T cells overturned: the effectors fight back. Immunology. 2009. 126: 466- 474.

59. de la,R.M., Rutz,S., Dorninger,H., and Scheffold,A., Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. eur.J.Immunol. 2004. 34: 2480-2488.

60. Zhang,H., Chua,K.S., Guimond,M., Kapoor,V., Brown,M.V., Fleisher,T.A., long,l.M., Bernstein,D., Hill,B.J., Douek,D.C., Berzofsky,J.A., Carter,C.S., Read,E.J., Helman,l.J., and Mackall,C.l., lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. nat. med. 2005. 11: 1238-1243.

61. Ahmadzadeh,M. and Rosenberg,S.A., Il-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood. 2006. 107: 2409-2414.

62. Zorn,E., Nelson,E.A., Mohseni,M., Porcheray,F., Kim,H., litsa,D., Bellucci,R., Raderschall,E., Canning,C., Soiffer,R.J., Frank,D.A., and Ritz,J., Il-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood. 2006. 108: 1571-1579.

63. van Amelsfort,J.M., van Roon,J.A., Noordegraaf,M., Jacobs,K.M., Bijlsma,J.W., lafeber,F.P., and Taams,l.S., Proinflammatory mediator-induced reversal of CD4+,CD25+ regulatory T cell-mediated suppression in rheumatoid arthritis. arthritis Rheum. 2007. 56: 732-742.

64. Valencia,X., Stephens,G., Goldbach-Mansky,R., Wilson,M., Shevach,E.M., and lipsky,P.E., TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood. 2006. 108: 253-261. 65. Chen,X., Baumel,M., Mannel,D.N., Howard,O.M., and Oppenheim,J.J., Interaction of TNF with

TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells. J.Immunol. 2007. 179: 154-161.

66. O’sullivan,B.J., Thomas,H.E., Pai,S., Santamaria,P., Iwakura,y., Steptoe,R.J., Kay,T.W., and Thomas,R., Il-1beta Breaks Tolerance through Expansion of CD25+ Effector T Cells. J.Immunol. 2006. 176: 7278-7287.

67. Peluso,I., Fantini,M.C., Fina,D., Caruso,R., Boirivant,M., MacDonald,T.T., Pallone,F., and Monteleone,G., Il-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes. J.Immunol. 2007. 178: 732-739.

68. Clough,l.E., Wang,C.J., Schmidt,E.M., Booth,G., Hou,T.Z., Ryan,G.A., and Walker,l.S., Release from regulatory T cell-mediated suppression during the onset of tissue-specific autoimmunity is associated with elevated Il-21. J.Immunol. 2008. 180: 5393-5401.

69. Koenen,H.J., Smeets,R.l., Vink,P.M., van,R.E., Boots,A.M., and Joosten,I., Human CD25highFoxp3pos regulatory T cells differentiate into Il-17-producing cells. Blood. 2008. 112: 2340-2352.

70. Beriou,G., Costantino,C.M., Ashley,C.W., yang,l., Kuchroo,V.K., Baecher-Allan,C., and Hafler,D.A., Il-17 producing human peripheral regulatory T cells retain suppressive function. Blood. 2009. 113:4240-4249.

71. Voo,K.S., Wang,y.H., Santori,F.R., Boggiano,C., Wang,y.H., Arima,K., Bover,l., Hanabuchi,S., Khalili,J., Marinova,E., Zheng,B., littman,D.R., and liu,y.J., Identification of Il-17-producing FOXP3+

regulatory T cells in humans. Proc.Natl.acad.sci.u.s.a. 2009. 106: 4793-4798.

72. Radhakrishnan,S., Cabrera,R., Schenk,E.l., Nava-Parada,P., Bell,M.P., Van,K., V, Marler,R.J., Felts,S.J., and Pease,l.R., Reprogrammed FoxP3+ T regulatory cells become Il-17+ antigen-specific autoimmune effectors in vitro and in vivo. J.Immunol. 2008. 181: 3137-3147.

73. yang,X.O., Nurieva,R., Martinez,G.J., Kang,H.S., Chung,y., Pappu,B.P., Shah,B., Chang,S.H., Schluns,K.S., Watowich,S.S., Feng,X.H., Jetten,A.M., and Dong,C., Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity. 2008. 29: 44-56.

74. Zhou,X., Jeker,l.T., Fife,B.T., Zhu,S., Anderson,M.S., McManus,M.T., and Bluestone,J.A., Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J.exp.Med. 2008. 205: 1983- 1991.

75. Hoffmann,P., Boeld,T.J., Eder,R., Huehn,J., Floess,S., Wieczorek,G., Olek,S., Dietmaier,W., Andreesen,R., and Edinger,M., loss of FOXP3 expression in natural human CD4(+)CD25(+) regulatory T cells upon repetitive in vitro stimulation. eur.J.Immunol. 2009. 39:1088-1097. 76. Vignali,D.A., Collison,l.W., and Workman,C.J., How regulatory T cells work. nat.rev.immunol.

2008. 8: 523-532.

77. yang,J., Brook,M.O., Carvalho-Gaspar,M., Zhang,J., Ramon,H.E., Sayegh,M.H., Wood,K.J., Turka,l.A., and Jones,N.D., Allograft rejection mediated by memory T cells is resistant to regulation. Proc.Natl.acad.sci.u.s.a. 2007. 104: 19954-19959.

78. Wing,K., Onishi,y., Prieto-Martin,P., yamaguchi,T., Miyara,M., Fehervari,Z., Nomura,T., and Sakaguchi,S., CTlA-4 control over Foxp3+ regulatory T cell function. science. 2008. 322: 271-275. 79. Grohmann,U., Orabona,C., fallarino,f., Vacca,C., Calcinaro,f., falorni,A., Candeloro,P.,

Belladonna,M.l., Bianchi,R., Fioretti,M.C., and Puccetti,P., CTlA-4-Ig regulates tryptophan catabolism in vivo. nat.immunol. 2002. 3: 1097-1101.

80. Munn,D.H., Sharma,M.D., and Mellor,A.l., ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2,3-dioxygenase activity in dendritic cells. J.Immunol. 2004. 172: 4100-4110. 81. Mellor,A.l., Baban,B., Chandler,P., Marshall,B., Jhaver,K., Hansen,A., Koni,P.A., Iwashima,M.,

and Munn,D.H., Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J.Immunol. 2003. 171: 1652-1655.

82. Chen,W., liang,X., Peterson,A.J., Munn,D.H., and Blazar,B.R., The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J.Immunol. 2008. 181: 5396-5404.

83. Collison,l.W., Workman,C.J., Kuo,T.T., Boyd,K., Wang,y., Vignali,K.M., Cross,R., Sehy,D., Blumberg,R.S., and Vignali,D.A., The inhibitory cytokine Il-35 contributes to regulatory T-cell function. nature. 2007. 450: 566-569.

84. Garin,M.I., Chu,C.C., Golshayan,D., Cernuda-Morollon,E., Wait,R., and lechler,R.I., Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood. 2007. 109: 2058-2065.

85. Perone,M.J., Bertera,S., Shufesky,W.J., Divito,S.J., Montecalvo,A., Mathers,A.R., larregina,A.T., Pang,M., seth,N., Wucherpfennig,K.W., Trucco,M., Baum,L.G., and Morelli,A.E., suppression of autoimmune diabetes by soluble galectin-1. J.Immunol. 2009. 182: 2641-2653.

86. yamagiwa,S., Gray,J.D., Hashimoto,S., and Horwitz,D.A., A role for TGF-beta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J.Immunol. 2001. 166:

In document Concreto celular para uso estructural (página 48-52)