The Roles of α4-Integrins in the Development of Insulin-Dependent Diabetes Mellitus

  • S. A. Michie
  • H.-K. Sytwu
  • J. O. McDevitt
  • X.-D. Yang
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 231)


Most lymphocytes recirculate throughout the body, migrating from blood through organized lymphoid tissues such as lymph nodes (LN) and Peyer’s patches (PP), then to lymph and back to blood (Gowans and Knight 1964). Smaller numbers of lymphocytes migrate from blood to extranodal tissues such as pancreas and then through lymphatic vessels to LN (Mackay et al. 1990). An important feature of this migration is the ability of lymphocytes to recognize and adhere to the surface of blood vessel endothelial cells before migrating through the vessel wall into surrounding tissue (Carlos and Harlan 1994; Imhof and Dunon 1995; Butcher and Picker 1996).


Lacrimal Gland Experimental Allergic Encephalomyelitis Nonobese Diabetic Mouse Lymphocyte Migration Lymphocyte Homing 
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  1. Asamoto H, Akazawa Y, Tashiro S, Oishi M, Azuma T, Koide S, Sudo K, Yokota H, Tochino Y (1984) Infiltration of lymphocytes in various organs of the NOD (non-obese diabetic) mouse. J Jpn Diabetic Soc 27: 775–781Google Scholar
  2. Bach J-F (1994) Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev 15: 516–542PubMedGoogle Scholar
  3. Bargatze RF, Jutila MA, Butcher EC (1995) Distinct roles of L-selectin and α4β7 and LFA-1 in lymphocyte homing to Peyer’s patch HEV in situ: the multistep model confirmed and refined. Immunity 3: 99–108PubMedCrossRefGoogle Scholar
  4. Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CA Jr (1993) Surface expression of α4 integrin by CD4+ T cells is required for their entry into brain parenchyma. J Exp Med 177: 57–68PubMedCrossRefGoogle Scholar
  5. Baron JL, Reich EP, Visintin I, Janeway CA Jr (1994) The pathogenesis of adoptive murine autoimmune diabetes requires an interaction between alpha 4-integrins and vascular cell adhesion molecule-1. J Clin Invest 93: 1700–1708PubMedCrossRefGoogle Scholar
  6. Barten DM, Ruddle NH (1994) Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis. J Neuroimmunol 51: 123–133PubMedCrossRefGoogle Scholar
  7. Baumhueter S, Singer MS, Henzel W, Hemmerich S, Renz M, Rosen SD, Lasky LA (1992) Binding of L-selectin to the vascular sialomucin CD34. Science 262: 436–438CrossRefGoogle Scholar
  8. Baumhueter S, Dybdal N, Kyle C, Lasky LA (1994) Global vascular expression of murine CD34, a sialomucin-like endothelial ligand for L-selectin. Blood 84 (8): 2554–2565PubMedGoogle Scholar
  9. Berlin C, Berg EL, Briskin MJ, Andrew DP, Kilshaw PJ, Holzmann B, Weissman IL, Hamann A, Butcher EC (1993) α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 74: 185–195Google Scholar
  10. Briskin MJ, McEvoy L, Butcher EC (1993) The mucosal vascular addressin, MAdCAM-1, displays homology to immunoglobulin and mucin-like adhesion receptors and to IgA. Nature 363: 461–464PubMedCrossRefGoogle Scholar
  11. Briskin MJ, Winsor-Hines D, Shyjan A, Bloom S, Wilson J, McEvoy LM, Butcher EC, Kassam N, MacKay CR, Newman W, Ringler DJ. Expression of human mucosal addressin molecule is restricted to intestinal tract and associated lymphoid tissue (submitted)Google Scholar
  12. Burkly LC, Jakubowski A, Hattori M (1994) Protection against adoptive transfer of autoimmune diabetes mediated through very late antigen-4 integrin. Diabetes 43: 529–534PubMedCrossRefGoogle Scholar
  13. Butcher EC (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67: 1033–1036PubMedCrossRefGoogle Scholar
  14. Butcher EC, Picker LJ (1996) Lymphocyte homing and homeostasis. Science 272: 60–66PubMedCrossRefGoogle Scholar
  15. Carlos TM, Harlan JM (1994) Leukocyte-endothelial adhesion molecules. Blood 84: 2068–2101PubMedGoogle Scholar
  16. Castano L, Eisenbarth GS (1990) Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol 8: 647–679PubMedCrossRefGoogle Scholar
  17. Chan BCM, Elices MJ, Murphy E, Hemler ME (1992) Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of α4β1 (VLA-4) and a4p7 on the human B cell line JY. J Biol Chem 267: 8366–8370PubMedGoogle Scholar
  18. Dawson J, Sedgwick AD, Edwards JCW, Lees P (1992) The monoclonal antibody MEL-14 can block lymphocyte migration into a site of chronic inflammation. Eur J Immunol 22: 1647–1650PubMedCrossRefGoogle Scholar
  19. Dopp JM, Breneman SM, Olschowka JA (1994) Expression of ICAM-1, VCAM-1, L-selectin, and leukosialin in the mouse central nervous system during the induction and remission stages of experimental allergic encephalomyelitis. J Neuroimmunol 54: 129–144Google Scholar
  20. Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR (1990) VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/ fibronectin binding site. Cell 60: 577–584PubMedCrossRefGoogle Scholar
  21. Engelhardt B, Martin-Simonet MTG, Rott L, Butcher EC, Michie SA. T lymphocytes present in sites of chronic inflammation can be distinguished by their expression of tissue-selective cell adhesion molecules (submitted)Google Scholar
  22. Fabien N, Bergerot I, Orgiazzi J, Thivolet C (1996) Lymphocyte function associated antigen-1, integrin alpha 4, and L-selectin mediate T-cell homing to the pancreas in the model of adoptive transfer of diabetes in NOD mice. Diabetes 45: 1181–1186PubMedCrossRefGoogle Scholar
  23. Faveeuw C, Gagnerault MC, Lepault F (1994) Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice. J Immunol 152: 5969–5978PubMedGoogle Scholar
  24. Faveeuw C, Gagnerault MC, Kraal G, Lepault F (1995) Homing of lymphocytes into islets of Langerhans in prediabetic non-obese diabetic mice is not restricted to autoreactive T cells. Int Immunol 7: 1905–1913PubMedCrossRefGoogle Scholar
  25. Fries JWU, Williams AJ, Atkins RC, Newman W, Lipscomb MF, Collins T (1993) Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation. Am J Pathol 143: 725–737PubMedGoogle Scholar
  26. Gallatin WM, Weissman IL, Butcher EC (1983) A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature 304: 30–34PubMedCrossRefGoogle Scholar
  27. Goldrath AW, Barber L, Chen KE, Alters SE (1995) Differences in adhesion markers, activation markers, and TCR in islet infiltrating vs peripheral lymphocytes in the NOD mouse. J Autoimmunity 8: 209–220CrossRefGoogle Scholar
  28. Gowans JL, Knight EJ (1964) The route of recirculation of lymphocytes in the rat. Proc R Soc Lond Biol Sci 159: 257–282CrossRefGoogle Scholar
  29. Hamann A, Jablonski-Westrich D, Duijvestijn A, Butcher EC, Baisch H, Harder R, Thiele H-G (1988) Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing. J Immunol 140: 693–699PubMedGoogle Scholar
  30. Hamann A, Andrew DP, Jablonski-Westrich D, Holzmann B, Butcher EC (1994) Role of ot4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol 152: 3282–3293PubMedGoogle Scholar
  31. Hanninen A, Jalkanen S, Salmi M, Toikkanen S, Nikolakaros G, Simell O (1992) Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus. J Clin Invest 90: 1901–1910Google Scholar
  32. Hanninen A, Taylor C, Streeter PR, Stark LS, Sarte JM, Shizuru JA, Simell O, Michie SA (1993) Vascular addressins are induced on islet vessels during insulitis in nonobese diabetic mice and are involved in lymphoid cell binding to islet endothelium. J Clin Invest 92: 2509–2515PubMedCrossRefGoogle Scholar
  33. Hanninen A, Salmi M, Simell O, Jalkanen S (1996) Mucosa-associated (beta 7-integrin high) lymphocytes accumulate early in the pancreas of NOD mice and show aberrant recirculation behavior. Diabetes 45: 1173–1180PubMedCrossRefGoogle Scholar
  34. Hasegawa Y, Yokono K, Taki T, Amano K, Tominaga Y, Yoneda R, Yagi N, Maeda S, Yagita H, Okumua K, Kasuga M (1994) Prevention of autoimmune insulin-dependent diabetes in non-obese diabetic mice by anti-LFA-1 and anti-ICAM-1 mAb. Int Immunol 6: 831–838PubMedCrossRefGoogle Scholar
  35. Hesterberg PE, Winsor-Hines D, Briskin MJ, Soler-Ferran D, Merrill C, Mackay CR, Newman W, Ringler DJ (1996) Rapid resolution of chronic colitis in the cotton-top tamarin with an antibody to a gut-homing integrin alpha4 beta7. Gastroenterology 11 1: 1373–1380CrossRefGoogle Scholar
  36. Higuchi Y, Herrera P, Muniesa PJH, Belin D, Ohashi P, Aichele P, Orci L, Vassalli J-D, Vassalli P (1992) Expression of a tumor necrosis factor a transgene in murine pancreatic β cells results in severe and permanent insulitis without evolution towards diabetes. J Exp Med 176: 1719–1731PubMedCrossRefGoogle Scholar
  37. Holzmann B, Mclntyre BW, Weissman IL: (1989) Identification of a murine Peyer’s patch specific lymphocyte homing receptor as an integrin molecule with an a chain homologous to human VLA-4a. Cell 56: 37–46PubMedCrossRefGoogle Scholar
  38. Hu MCT, Crowe DT, Weissman IL, Holzmann B (1992) Cloning and expression of mouse integrin ßp(β7): a functional role in Peyer’s patch-specific lymphocyte homing. Proc Natl Acad Sci USA 89: 8254–8258PubMedCrossRefGoogle Scholar
  39. Hunger RE, Muller S, Laissue JA, Hess MW, Carnaud C, Garcia I, Mueller C (1996) Inhibition of submandibular and lacrimal gland infiltration in nonobese diabetic mice by transgenic expression of soluble TNF-receptor p55. J Clin Invest 98: 954–961PubMedCrossRefGoogle Scholar
  40. Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69: 11–25PubMedCrossRefGoogle Scholar
  41. Imhof BA, Dunon D (1995) Leukocyte migration and adhesion. Adv Immunol 58: 345–416PubMedCrossRefGoogle Scholar
  42. Jacobsen K, Kravitz J, Kincade PW et al (1996) Adhesion receptors on bone marrow stromal cells: in vivo expression of vascular cell adhesion molecule-1 by reticular cells and sinusoidal endothelium in normal and gamma-irradiated mice. Blood 87: 73–82PubMedGoogle Scholar
  43. Jakubowski A, Ehrenfels BN, Pepinsky RB, Burkly LC (1995) Vascular cell adhesion molecule-Ig fusion protein selectively targets activated alpha 4-integrin receptors in vivo. Inhibition of autoimmune diabetes in an adoptive transfer model in nonobese diabetic mice. J Immunol 155: 938–946Google Scholar
  44. Kilshaw PJ, Murant SJ (1991) Expression and regulation of β7 (βp) integrins on mouse lymphocytes: relevance to the mucosal immune system. Eur J Immunol 21: 2591–2597PubMedCrossRefGoogle Scholar
  45. Koch AE, Burrows JC, Haines GK, Carlos TM, Harlan JM, Leibovich SJ (1991) Immunolocalization of endothelial and leukocyte adhesion molecules in human rheumatoid and osteoarthritic synovial tissues. Lab Invest 64: 313–320PubMedGoogle Scholar
  46. Kraal G, Schornagel K, Streeter PR et al (1995) Expression of the mucosal vascular addressin, MAd-CAM-1, on sinus-lining cells in the spleen. Am J Pathol 147: 763–771PubMedGoogle Scholar
  47. Kratz A, Campos-Neto A, Hanson MS, Ruddle NH (1996) Chronic inflammation caused by lympho-toxin is lymphoid neogenesis. J Exp Med 183: 1461–1472PubMedCrossRefGoogle Scholar
  48. Kuchroo VK, Martin CA, Greer JM, Ju ST, Sobel RA, Dorf ME (1993) Cytokines and adhesion molecules contribute to the ability of myelin proteolipid protein-specific T cell clones to mediate experimental allergic encephalomyelitis. J Immunol 151: 4371–4382PubMedGoogle Scholar
  49. Lasky LA, Singer MS, Dowbenko D, Imai Y, Henzel WJ, Grimley C, Fennie C, Gillett N, Watson SR, Rosen SD (1992) An endothelial ligand for L-selectin is a novel mucin-like molecule. Cell 69: 927–938PubMedCrossRefGoogle Scholar
  50. Lee MS, Sarvetnick N (1994) Induction of vascular addressins and adhesion molecules in the pancreas of IFN-gamma transgenic mice. J Immunol 152: 4597–4603PubMedGoogle Scholar
  51. Lepault F, Gagnerault MC, Faveeuw C, Bazin H, Boitard C (1995) Lack of L-selectin expression by cells transferring diabetes in NOD mice: insights into the mechanisms involved in diabetes prevention by MEL-14 antibody treatment. Eur J Immunol 25: 1502–1507PubMedCrossRefGoogle Scholar
  52. Lobb RR, Hemler ME (1994) The pathophysiologic role of a4-Integrins in vivo. J Clin Invest 94: 1722–1728PubMedCrossRefGoogle Scholar
  53. Lo D, Reilly CR, Scott B, Liblau R, McDevitt HO, Burkly LC (1993) Antigen-presenting cells in adoptively transferred and spontaneous autoimmune diabetes. Eur J Immunol 23: 1693–1698PubMedCrossRefGoogle Scholar
  54. Mackay CR, Marston WL, Dudler L (1990) Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med 171: 801–817PubMedCrossRefGoogle Scholar
  55. Mebius RE, Breve J, Kraal G, Streeter PR (1993) Developmental regulation of vascular addressin expression: a possible role for site-associated environments. Int Immunol 5: 443–449PubMedCrossRefGoogle Scholar
  56. Michie SA, Rouse RV (1991) Traffic of peripheral B and T lymphocytes to hyperplastic, preneoplastic thymuses of AKR mice. Am J Pathol 138: 1015–1025PubMedGoogle Scholar
  57. Michie SA, Streeter PR, Butcher EC, Rouse RV (1995) L-selectin and α4β7 integrin homing receptor pathways mediate peripheral lymphocyte traffic to AKR mouse hyperplastic thymus. Am J Pathol 147: 412–421PubMedGoogle Scholar
  58. Miyake K, Medina K, Ishihara K, Kimoto M, Auerbach R, Kincade PW (1991) A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture. J Cell Biol 114: 557–565PubMedCrossRefGoogle Scholar
  59. Moriyama H, Yokono K, Amano K, Nagata M, Hasegawa Y, Okamoto N, Tsukamoto K, Miki M, Yoneda R, Yagi N et al (1996) Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway. J Immunol 157: 3737–3743PubMedGoogle Scholar
  60. O’Neill JK, Butter C, Baker D, Gschmeissner SE, Kraal G, Butcher EC, Turk JL (1991) Expression of vascular addressins and ICAM-1 by endothelial cells in the spinal cord during chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse. Immunology 72: 520–525PubMedGoogle Scholar
  61. Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA (1993) Transgenic tumor necrosis factor ( TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. J Immunol 150: 4136–4150Google Scholar
  62. Picarella D, Hurlbut P, Rottman J, Shi X, Butcher E, Ringler DJ (1997) Monoclonal antibodies specific for β7 integrin and MAdCAM-1 reduce inflammation in the colon of seid mice reconstituted with CD45RBhi CD4+ T cells. J Immunol 158: 2099–2106PubMedGoogle Scholar
  63. Postigo AA, Teixido J, Sanchez-Madrid F (1993) The alpha 4 beta 1/VCAM-l adhesion pathway in physiology and disease. Res Immunol 144: 723–735PubMedCrossRefGoogle Scholar
  64. Rice GE, Munro JM, Corless C, Bevilacqua MP (1991) Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflammed human tissues. Am J Pathol 138: 385–393Google Scholar
  65. Rossini AA, Greiner DL, Friedmen HP, Mordes JP (1993) Immunopathogenesis of diabetes mellitus. Diabetes Rev 1: 43–75Google Scholar
  66. Ruegg C, Postigo AA, Sikorski EE, Butcher EC, Pytela R, Erle DJ (1992) Role of integrin alpha 4/beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering. J Cell Biol 117: 179–189PubMedCrossRefGoogle Scholar
  67. Shimizu Y, Newman W, Tanaka Y, Shaw S (1992) Lymphocyte interactions with endothelial cells. Immunol Today 13: 106–112PubMedCrossRefGoogle Scholar
  68. Sikorski EE, Hallmann R, Berg EL, Butcher EC (1993) The Peyer’s patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by TNF-a and IL-1. J Immunol 151: 5239–5250PubMedGoogle Scholar
  69. Somoza N, Vargas F, Roura-Mir C, Vives-Pi M, Fernandez-Figueras MT, Ariza A, Gomis R, Bragado R, Marti M, Jaraquemada D, Pujol-Borrell R (1994) Pancreas in recent onset insulin-dependent diabetes mellitus. Changes in HLA, adhesion molecules and autoantigens, restricted T cell receptor Vβ usage, and cytokine profile. J Immunol 153: 1360–1377Google Scholar
  70. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76: 301–314PubMedCrossRefGoogle Scholar
  71. Stamper HB Jr, Woodruff JJ (1976) Lymphocyte homing into lymph nodes. In vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules. J Exp Med 144: 828–833Google Scholar
  72. Steffen BJ, Butcher EC, Engelhardt B (1994) Evidence for involvement of ICAM-1 and VCAM-1 in lymphocyte interaction with endothelium in experimental autoimmune encephalomyelitis in the central nervous system in the SJL/J mouse. Am J Pathol 145: 189–201PubMedGoogle Scholar
  73. Streeter PR, Rouse BT, Butcher EC (1988a) Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes. J Cell Biol 107: 1853–1862PubMedCrossRefGoogle Scholar
  74. Streeter PR, Berg EL, Rouse BTW, Bargatze RK, Butcher EC (1988b) A tissue specific endothelial cell molecule involved in lymphocyte homing. Nature 331: 41–46PubMedCrossRefGoogle Scholar
  75. Szabo MC, Butcher EC, McEvoy LM (1997) Specialization of mucosal follicular dendritic cells revealed by mucosal addressin-cell adhesion molecule-1 display. J Immunol 158: 5584–5588PubMedGoogle Scholar
  76. Tsukamoto K, Yokono K, Amano K, Nagata M, Yagi N, Tominaga Y, Moriyama H, Miki M, Okamoto N, Yoneda R et al (1995) Administration of monoclonal antibodies against vascular cell adhesion molecule-1/very late antigen-4 abrogates predisposing autoimmune diabetes in NOD mice. Cell Im¬munol 165: 193–201CrossRefGoogle Scholar
  77. Wayner EA, Garcia-Pardo A, Humphries MJ, McDonald JA, Carter WG (1989) Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain ( CS-l) in plasma fibronectin. J Cell Biol 109: 1321–1330Google Scholar
  78. Weller RO, Engelhardt B, Phillips MJ (1996) Lymphocyte targeting of the central nervous system: a review of afferent and efferent CNS-immune pathways. Brain Pathol 6: 275–288PubMedCrossRefGoogle Scholar
  79. Wogensen L, Huang X, Sarvetnick N (1993) Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukin 10 in the islets of Langerhans. J Exp Med 178: 175–185PubMedCrossRefGoogle Scholar
  80. Yagi N, Yokono K, Amano K, Nagata M, Tsukamoto K, Hasegawa Y, Yoneda R, Okamoto N, Moriyama H, Miki M et al (1995) Expression of intercellular adhesion molecule 1 on pancreatic beta-cells accelerates beta-cell destruction by cytotoxic T-cells in murine autoimmune diabetes. Diabetes 44: 744–752PubMedCrossRefGoogle Scholar
  81. Yang X-D, Karin N, Tisch R, Steinman L, McDevitt HO (1993) Inhibition of insulitis and prevention of diabetes in nonobese diabetic mice by blocking L-selectin and very late antigen-4 adhesion receptors. Proc Natl Acad Sci USA 90: 10494–10498PubMedCrossRefGoogle Scholar
  82. Yang X-D, Michie SA, Karin N, Tisch R, Steinman L, McDevitt HO (1994a) A predominant role of integrin a4 in the spontaneous development of autoimmune diabetes in nonobese diabetic mice. Proc Natl Acad Sci USA 91: 12604–12608PubMedCrossRefGoogle Scholar
  83. Yang X-D, Tisch R, Singer SM, Cao ZA, Liblau R, Schreiber RD, McDevitt HO (1994b) Effect of tumor necrosis factor a on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and diabetogenic process. J Exp Med 180: 995–1004Google Scholar
  84. Yang X-D, Sytwu H-K, McDevitt HO, Michie SA. Involvement of beta7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the development of diabetes in nonobese diabetic mice. Diabetes (in press)Google Scholar
  85. Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin. Nature 356: 63–66PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • S. A. Michie
    • 1
    • 2
  • H.-K. Sytwu
    • 3
  • J. O. McDevitt
    • 3
    • 4
  • X.-D. Yang
    • 5
  1. 1.Department of Veterans AffairsPalo Alto Health Care System, Center for Molecular Biology in MedicinePalo AltoUSA
  2. 2.Department of PathologyStanford University School of MedicineStanfordUSA
  3. 3.Department of Microbiology and ImmunologyStanford University School of MedicineStanfordUSA
  4. 4.Department of MedicineStanford University School of MedicineStanfordUSA
  5. 5.Division of Preclinical ResearchAbgenix, Inc.FremontUSA

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