Engineering humanized mice for improved hematopoietic reconstitution

Cellular and Molecular Immunology

Volumn 9, Issue 3, 2012, Pages 215-224

  Drake, Adam C ^a   Chen, Qingfeng ^b   Chen, Jianzhu ^a,b  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b SINGAPORE MIT ALLIANCE FOR RESEARCH AND TECHNOLOGY   (Singapore)

Author keywords

cytokines; expansion; genetic modification; hematopoietic stem cells; humanized mice

Indexed keywords

COLONY STIMULATING FACTOR 1; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 15; INTERLEUKIN 15 RECEPTOR ALPHA; INTERLEUKIN 18; INTERLEUKIN 3; INTERLEUKIN 4; INTERLEUKIN 7; LENTIVIRUS VECTOR; NOTCH RECEPTOR;

ANIMAL CELL; B LYMPHOCYTE; BAGG ALBINO MOUSE; CD34 SELECTION; CELL CULTURE; CELL DIFFERENTIATION; CELL EXPANSION; CELL INTERACTION; CELL LINEAGE; CELL PROLIFERATION; CELL SURVIVAL; CELL TRANSPORT; COCULTURE; DNA MODIFICATION; HEMATOPOIETIC STEM CELL; HUMANIZED MICE; IMMUNE DEFICIENCY; IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME; MOUSE; MOUSE STRAIN; NATURAL KILLER CELL; NONHUMAN; NONOBESE DIABETIC MOUSE; PERIPHERAL BLOOD STEM CELL; PLASMID; REVIEW; SCID MOUSE; T LYMPHOCYTE;

ANIMALS; CELL SURVIVAL; CYTOKINES; GENETIC ENGINEERING; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOMODULATION; MICE; MICE, MUTANT STRAINS; MICE, SCID; RESEARCH DESIGN; STEM CELL NICHE; TRANSPLANTATION, HETEROLOGOUS;

ANIMALIA; MUS;

EID: 84860861758     PISSN: 16727681     EISSN: None     Source Type: Journal    
DOI: 10.1038/cmi.2012.6     Document Type: Review

References (90)

1. Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K et al. NOD/SCID/ cc null mouse: an excellent recipient mouse model for engraftment of human cells. Blood 2002; 100: 3175-3182. (Pubitemid 35217065)
2. Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti JC, Lanzavecchia A et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 2004; 304: 104-107. (Pubitemid 38451466)
3. Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor c chainnull mice. Blood 2005; 106: 1565-1573. (Pubitemid 41208567)
4. Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R cnull mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005; 174: 6477-6489. (Pubitemid 40663843)
5. McDermott SP, Eppert K, Lechman ER, Doedens M, Dick JE. Comparison of human cord blood engraftment between immunocompromised mouse strains. Blood 2010; 116: 193-200.
6. Chen Q, Khoury M, Chen J. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. Proc Natl Acad Sci USA 2009; 106: 21783-21788.
7. Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research. Nat Rev Immunol 2007; 7: 118-130. (Pubitemid 46174859)
8. Billerbeck E, Barry WT, Mu K, Dorner M, Rice CM, Ploss A. Development of human CD41FoxP31 regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2Rcnull humanized mice. Blood 2011; 117: 3076-3086.
9. Rongvaux A, Willinger T, Takizawa H, Rathinam C, Auerbach W, Murphy AJ et al. Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. Proc Natl Acad Sci USA 2011; 108: 2378-2383.
10. Willinger T, Rongvaux A, Takizawa H, Yancopoulos GD, Valenzuela DM, Murphy AJ et al. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. Proc Natl Acad Sci USA 2011; 108: 2390-2395.
11. Rathinam C, Poueymirou WT, Rojas J, Murphy AJ, Valenzuela DM, Yancopoulos GD et al. Efficient differentiation and function of human macrophages in humanized CSF-1 mice. Blood 2011; 118: 3119-3128.
12. Shultz LD, Saito Y, Najima Y, Tanaka S, Ochi T, Tomizawa M et al. Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r cnull humanized mice. Proc Natl Acad Sci USA 2010; 107: 13022-13027.
13. Jaiswal S, Pearson T, FribergH, Shultz LD, Greiner DL, Rothman AL et al. Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NODscid IL2rcnull mice.PLoS One 2009; 4: e7251.
14. Danner R, Chaudhari SN, Rosenberger J, Surls J, Richie TL, Brumeanu TD et al. Expression of HLA class II molecules in humanized NOD.Rag1KO. IL2RgcKO mice is critical for development and function of human T and B cells. PLoS One 2011; 6: e19826.
15. Covassin L, Laning J, Abdi R, Langevin DL, Phillips NE, Shultz LD et al. Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rcnull H2-Ab1 (tm1Gru) Tg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease. Clin Exp Immunol 2011; 166: 269-280.
16. Takenaka K, Prasolava TK, Wang JC, Mortin-Toth SM, Khalouei S, Gan OI et al. Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol 2007; 8: 1313-1323. (Pubitemid 350138972)
17. Chao MP, Alizadeh AA, Tang C, Myklebust JH, Varghese B, Gill S et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non- Hodgkin lymphoma. Cell 2010; 142: 699-713.
18. Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD Jr et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 2009; 138: 286-299.
19. Jaiswal S, Jamieson CH, Pang WW, Park CY, Chao MP, Majeti R et al. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell 2009; 138: 271-285.
20. Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C, Philbrick W et al. Transgenic expression of human signal regulatory protein alpha in Rag22/2cc 2/2 mice improves engraftment of human hematopoietic cells in humanized mice. Proc Natl Acad Sci USA 2011; 108: 13218-13223.
21. Notta F, Doulatov S, LaurentiE, Poeppl A, Jurisica I,Dick JE. Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science 2011; 333: 218-21.
22. Majeti R, Park CY, Weissman IL. Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. Cell Stem Cell 2007; 1: 635-645. (Pubitemid 350215330)
23. Drake AC, Khoury M, Leskov I, Iliopoulou BP, Fragoso M, Lodish H et al. Human CD341CD1331 hematopoietic stem cells cultured with growth factors including Angptl5 efficiently engraft adult NOD-SCID Il2rc2/2 (NSG) mice. PLoS One 2011; 6: e18382.
24. de Wynter EA, Buck D, Hart C, Heywood R, Coutinho LH, Clayton A et al. CD341AC1331 cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors. Stem Cells 1998; 16: 387-396. (Pubitemid 28524504)
25. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997; 90: 5002-5012. (Pubitemid 28007217)
26. Matsumura T, Kametani Y, Ando K, Hirano Y, Katano I, Ito R et al. Functional CD51 B cells develop predominantly in the spleen of NOD/SCID/ccnull (NOG) mice transplanted either with human umbilical cord blood, bone marrow, or mobilized peripheral blood CD341 cells. Exp Hematol 2003; 31: 789-797. (Pubitemid 37075972)
27. Hayakawa J, Hsieh MM, Uchida N, Phang O, Tisdale JF. Busulfan produces efficient human cell engraftment in NOD/LtSz-Scid IL2Rcnull mice. Stem Cells 2009; 27: 175-182.
28. Zhang L, Kovalev GI, Su L. HIV-1 infection and pathogenesis in a novel humanized mouse model. Blood 2007; 109: 2978-2981. (Pubitemid 46482096)
29. Jiang Q, Zhang L, Wang R, Jeffrey J, Washburn ML, Brouwer D et al. FoxP31CD41 regulatory T cells play an important role in acute HIV-1 infection in humanized Rag22/2cC2/2 mice in vivo. Blood 2008; 112: 2858-2868.
30. Zhang CC, Lodish HF. Cytokines regulating hematopoietic stem cell function. Curr Opin Hematol 2008; 15: 307-311.
31. Koestenbauer S, Zisch A, Dohr G, Zech NH. Protocols for hematopoietic stem cell expansion from umbilical cord blood. Cell Transplant 2009; 18: 1059-1068.
32. Dahlberg A, Delaney C, Bernstein ID. Ex vivo expansion of human hematopoietic stem and progenitor cells. Blood 2011; 117: 6083-6090.
33. Giassi LJ, Pearson T, Shultz LD, Laning J, Biber K, Kraus M et al. Expanded CD341 human umbilical cord blood cells generate multiple lymphohematopoietic lineages in NOD-scid IL2rcnull mice. Exp Biol Med (Maywood) 2008; 233: 997-1012.
34. Khoury M, Drake A, Chen Q, Dong D, Leskov I, Fragoso MF et al. Mesenchymal stem cells secreting angiopoietin-like-5 support efficient expansion of human hematopoietic stem cells without compromising their repopulating potential. Stem Cells Dev 2011; 20: 1371-1381.
35. Zhang CC, Kaba M, Iizuka S, Huynh H, Lodish HF. Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation. Blood 2008; 111: 3415-3423.
36. Boitano AE, Wang J, Romeo R, Bouchez LC, Parker AE, Sutton SE et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells. Science 2010; 329: 1345-1348.
37. Chou S, Chu P, Hwang W, Lodish H. Expansion of human cord blood hematopoietic stem cells for transplantation. Cell Stem Cell 2010; 7: 427-428.
38. Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RL, Bernstein ID. Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 2010; 16: 232-236.
39. Himburg HA, Muramoto GG, Daher P, Meadows SK, Russell JL, Doan P et al. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat Med 2010; 16: 475-482.
40. Yang H, Robinson SN, Lu J, Decker WK, Xing D, Steiner D et al. CD31 and/or CD141 depletion from cord blood mononuclear cells before ex vivo expansion culture improves total nucleated cell and CD341 cell yields. Bone Marrow Transplant 2010; 45: 1000-1007.
41. Frecha C, Costa C, NegreD, Amirache F, Trono D, Rio P et al. A novel lentivector targets gene transfer into hHSC in marrow from patients with BM-failure-syndrome and in vivo in humanized mice. Blood 2012; 119:1139-1150.
42. Novershtern N, Subramanian A, Lawton LN, Mak RH, Haining WN, McConkey ME et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell 2011; 144: 296-309.
43. Alexander IE, Russell DW, Miller AD. Transfer of contaminants in adeno-associated virus vector stocks can mimic transduction and lead to artifactual results. Hum Gene Ther 1997; 8: 1911-1920. (Pubitemid 27499664)
44. Zhou SZ, Cooper S, Kang LY, Ruggieri L, Heimfeld S, Srivastava A et al. Adenoassociated virus 2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood. J Exp Med 1994; 179: 1867-1875. (Pubitemid 24155667)
45. Nathwani AC, Hanawa H, Vandergriff J, Kelly P, Vanin EF, Nienhuis AW. Efficient gene transfer into human cord blood CD341 cells and the CD341CD382 subset using highly purified recombinant adeno-associated viral vector preparations that are free of helper virus and wild-type AAV. Gene Ther 2000; 7: 183-195. (Pubitemid 30113766)
46. Santat L, Paz H, Wong C, Li L, Macer J, Forman S et al. Recombinant AAV2 transduction of primitive human hematopoietic stem cells capable of serial engraftment in immune-deficient mice. Proc Natl Acad Sci USA 2005; 102: 11053-11058. (Pubitemid 41105991)
47. Hargrove PW, Vanin EF, Kurtzman GJ,Nienhuis AW. High-level globin gene expression mediated by a recombinant adeno-associated virus genome that contains the 39 c globin gene regulatory element and integrates as tandem copies in erythroid cells. Blood 1997; 89: 2167-2175. (Pubitemid 27132135)
48. Malik P, McQuiston SA, Yu XJ, Pepper KA, KrallWJ, Podsakoff GMet al. Recombinant adeno-associated virus mediates a high level of gene transfer but less efficient integration in the K562 human hematopoietic cell line. J Virol 1997; 71: 1776-1783. (Pubitemid 27078553)
49. Paz H, Wong CA, Li W, Santat L, Wong KK, Chatterjee S. Quiescent subpopulations of human CD34-positive hematopoietic stem cells are preferred targets for stable recombinant adeno-associated virus type 2 transduction. Hum Gene Ther 2007; 18: 614-626. (Pubitemid 47187093)
50. Srivastava A. Adeno-associated virus-mediated gene transfer. J Cell Biochem 2008; 105: 17-24.
51. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000; 288: 669-672. (Pubitemid 30241569)
52. Kaiser J. Gene therapy. Seeking the cause of induced leukemias in X-SCID trial. Science 2003; 299: 495. (Pubitemid 36135119)
53. Hacein-Bey-Abina S, von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003; 302: 415-419. (Pubitemid 37296260)
54. Pike-Overzet K, de Ridder D, Weerkamp F, Baert MR, Verstegen MM, Brugman MH et al. Gene therapy: is IL2RG oncogenic in T-cell development? Nature 2006; 443: E5; discussion E6-7.
55. Barabe F, Kennedy JA, Hope KJ, Dick JE. Modeling the initiation and progression of human acute leukemia in mice. Science 2007; 316: 600-604. (Pubitemid 46683146)
56. Hanawa H, Persons DA, Nienhuis AW. Mobilization and mechanism of transcription of integrated self-inactivating lentiviral vectors. J Virol 2005; 79: 8410-8421. (Pubitemid 40853543)
57. Chang AH, Sadelain M. The genetic engineering of hematopoietic stem cells: the rise of lentiviral vectors, the conundrum of the ltr, and the promise of lineage-restricted vectors. Mol Ther 2007; 15: 445-456.
58. Karlsson S, Ooka A, Woods NB. Development of gene therapy for blood disorders by gene transfer into haematopoietic stem cells. Haemophilia 2002; 8: 255-260. (Pubitemid 35277144)
59. Kissler S, Stern P, Takahashi K, Hunter K, Peterson LB, Wicker LS. In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes. Nat Genet 2006; 38: 479-483.
60. Marodon G, Mouly E,Blair EJ, Frisen C, Lemoine FM, Klatzmann D. Specific transgene expression in human and mouse CD41 cells using lentiviral vectors with regulatory sequences from the CD4 gene. Blood 2003; 101: 3416-3423. (Pubitemid 36857923)
61. Moreau T, Bardin F, Imbert J, Chabannon C, Tonnelle C. Restriction of transgene expression to the B-lymphoid progeny of human lentivirally transduced CD341 cells. Mol Ther 2004; 10: 45-56. (Pubitemid 38878148)
62. Moreau T, Barlogis V, Bardin F, Nunes JA, Calmels B, Chabannon C et al. Development of an enhanced B-specific lentiviral vector expressing BTK: a tool for gene therapy of XLA. Gene Ther 2008; 15: 942-952. (Pubitemid 351791481)
63. Sather BD, Ryu BY, Stirling BV, Garibov M, Kerns HM, Humblet-Baron S et al. Development of B-lineage predominant lentiviral vectors for use in genetic therapies for B cell disorders. Mol Ther 2011; 19: 515-525.
64. Cui Y, Golob J, Kelleher E, Ye Z, Pardoll D, Cheng L. Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells. Blood 2002; 99: 399-408. (Pubitemid 34533073)
65. Shi Q, Wilcox DA, Morateck PA, Fahs SA, Kenny D, Montgomery RR. Targeting platelet GPIbalpha transgene expression to human megakaryocytes and forming a complete complex with endogenous GPIbb and GPIX. J ThrombHaemost 2004; 2: 1989-1997. (Pubitemid 40192753)
66. Kanaji S, Kuether EL, Fahs SA, Schroeder JA, Ware J, MontgomeryRRet al. Correction of murine bernard-soulier syndrome by lentivirus-mediated gene therapy. Mol Ther 2011.
67. Perumbeti A, Higashimoto T, Urbinati F, Franco R, Meiselman HJ, Witte D et al. A novel human c-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction. Blood 2009; 114: 1174-1185.
68. Puthenveetil G, Scholes J, Carbonell D, Qureshi N, Xia P, Zeng L et al. Successful correction of the human b-thalassemia major phenotype using a lentiviral vector. Blood 2004; 104: 3445- 3453.2004 (Pubitemid 39564412)
69. Zhang F, Frost AR, Blundell MP, Bales O, Antoniou MN, Thrasher AJ. A ubiquitous chromatin opening element (UCOE) confers resistance to DNA methylation-mediated silencing of lentiviral vectors. Mol Ther 2010; 18: 1640-1649.
70. Leuci V, Gammaitoni L, Capellero S, Sangiolo D, Mesuraca M, BondHMet al. Efficient transcriptional targeting of human hematopoietic stem cells and blood cell lineages by lentiviral vectors containing the regulatory element of the Wiskott-Aldrich syndrome gene. Stem Cells 2009; 27: 2815-2823.
71. Levin MC, Lidberg U, Jirholt P, AdielsM,Wramstedt A, Gustafsson K et al. Evaluation of macrophage-specific promoters using lentiviral delivery in mice. Gene Ther; e-pub ahead of print 1 December 2011; doi: 10.1038/gt.2011.195.
72. O'Reilly D, Quinn CM, El-Shanawany T, Gordon S, Greaves DR. Multiple Ets factors and interferon regulatory factor-4 modulate CD68 expression in a cell type-specific manner. J Biol Chem 2003; 278: 21909-21919. (Pubitemid 36792598)
73. Krowka JF, Sarin S, Namikawa R, McCune JM, Kaneshima H. Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent. J Immunol 1991; 146: 3751-3756.
74. McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science 1988; 241: 1632-1639.
75. Dao MA, Pepper KA, Nolta JA. Long-term cytokine production from engineered primary human stromal cells influences human hematopoiesis in an in vivo xenograft model. Stem Cells 1997; 15: 443-454. (Pubitemid 27513719)
76. Kamel-Reid S, Dick JE. Engraftment of immune-deficient mice with human hematopoietic stem cells. Science 1988; 242: 1706-1709. (Pubitemid 19022179)
77. Lapidot T, Pflumio F, Doedens M, Murdoch B, Williams DE, Dick JE. Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice. Science 1992; 255: 1137-1141.
78. Vormoor J, Lapidot T, Pflumio F, Risdon G, Patterson B, Broxmeyer HE et al. Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice. Blood 1994; 83: 2489-2497. (Pubitemid 24135840)
79. Larochelle A, Vormoor J, Hanenberg H, Wang JC, Bhatia M, Lapidot T et al. Identification of primitive human hematopoietic cells capable of repopulating NOD/ SCID mouse bone marrow: implications for gene therapy. Nat Med 1996; 2: 1329-1337.
80. Mazurier F, Fontanellas A, Salesse S, Taine L, Landriau S, Moreau-Gaudry F et al. A novel immunodeficient mouse model-RAG2 x common cytokine receptor c chain double mutants-requiring exogenous cytokine administration for human hematopoietic stem cell engraftment. J Interferon Cytokine Res 1999; 19: 533-541. (Pubitemid 29269944)
81. Kalberer CP, Siegler U, Wodnar-Filipowicz A. Human NK cell development in NOD/ SCID mice receiving grafts of cord blood CD341 cells. Blood 2003; 102: 127-135. (Pubitemid 36759645)
82. Legrand N, WeijerK, Spits H. Experimental models to study development and function of the human immune system in vivo. J Immunol 2006; 176: 2053-2058. (Pubitemid 43201649)
83. Carballido JM, Namikawa R, Carballido-Perrig N, Antonenko S, Roncarolo MG, de Vries JE. Generation of primary antigen-specific human T- and B-cell responses in immunocompetent SCID-hu mice. Nat Med 2000; 6: 103-106. (Pubitemid 30048536)
84. Huntington ND, Legrand N, Alves NL, Jaron B, Weijer K, Plet A et al. IL-15 transpresentation promotes human NK cell development and differentiation in vivo. J Exp Med 2009; 206: 25-34.
85. Wege AK, Ernst W, Eckl J, Frankenberger B, Vollmann-Zwerenz A, Mannel DN et al. Humanized tumor mice-A new model to study and manipulate the immune response in advanced cancer therapy. Int J Cancer; e-pub ahead of print 4 May 2011; doi:10.1002/ijc.26159.
86. Pek EA, Chan T, Reid S, Ashkar AA. Characterization and IL-15 dependence of NK cells in humanized mice. Immunobiology 2011; 216: 218-224.
87. van Lent AU, Dontje W, Nagasawa M, Siamari R, Bakker AQ, Pouw SM et al. IL-7 enhances thymic human T cell development in 'human immune system' Rag22/2IL- 2Rcc2/2 mice without affecting peripheral T cell homeostasis. J Immunol 2009; 183: 7645-7655.
88. Senpuku H, Asano T, Matin K, Salam MA, Tsuha Y, Horibata S et al. Effects of human interleukin-18 and interleukin-12 treatment on human lymphocyte engraftment in NOD-scid mouse. Immunology. 2002; 107: 232-242. (Pubitemid 35279050)
89. Huntington ND, Alves NL, Legrand N, Lim A, Strick-Marchand H, Mention JJ et al. IL- 15 transpresentation promotes both human T-cell reconstitution and T-celldependent antibody responses in vivo. Proc Natl Acad Sci USA 2011; 108: 6217-6222.
90. Hu Z, van Rooijen N, Yang YG. Macrophages prevent human red blood cell reconstitution in immunodeficient mice. Blood 2011; 118: 5938-5946.