Dendritic cell immunotherapy for HIV infection: From theory to reality

Immunotherapy

Volumn 1, Issue 6, 2009, Pages 1039-1051

  Oshiro, Telma Miyuki ^a   De Almeida, Alexandre ^a   Duarte, Alberto José Da Silva ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

Dendritic cell; HIV infection; Therapeutic vaccine

Indexed keywords

ALPHA INTERFERON; CD40 LIGAND; DENDRITIC CELL VACCINE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HUMAN IMMUNODEFICIENCY VIRUS ANTIGEN; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; IMMUNOMODULATING AGENT; INTERLEUKIN 1BETA; INTERLEUKIN 4; INTERLEUKIN 6; PROSTAGLANDIN E2; RECOMBINANT PROTEIN; SYNTHETIC PEPTIDE; TUMOR NECROSIS FACTOR ALPHA;

CLINICAL PROTOCOL; CLINICAL TRIAL; DENDRITIC CELL; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOTHERAPY; NONHUMAN; PRIORITY JOURNAL; REVIEW; VACCINATION; VIRUS INACTIVATION; VIRUS PARTICLE;

AIDS VACCINES; ANIMALS; ANTIGEN PRESENTATION; CELL DIFFERENTIATION; DENDRITIC CELLS; HIV ANTIGENS; HIV INFECTIONS; HUMANS; IMMUNOTHERAPY, ADOPTIVE; LYMPHOCYTE ACTIVATION;

EID: 77953381819     PISSN: 1750743X     EISSN: None     Source Type: Journal    
DOI: 10.2217/imt.09.68     Document Type: Review

References (114)

1. Steinman RM, Cohn ZA: Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137(5), 1142-1162 (1973).
2. Inaba K, Metlay JP, Crowley MT, Steinman RM: Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J. Exp. Med. 172(2), 631-640 (1990). ■ Initial evidence of immunogenicity induced by dendritic cells (DCs).
3. Inaba K, Inaba M, Naito M, Steinman RM: Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo. J. Exp. Med. 178(2), 479-488 (1993).
4. Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 392(6673), 245-252 (1998). ■■ Review on aspects of the DCs immunobiology.
5. Fajardo-Moser M, Berzel S, Moll H: Mechanisms of dendritic cell-based vaccination against infection. Int. J. Med. Microbiol. 298(1-2), 11-20 (2008).
6. Coley WB: The treatment of malignant tumors by repeated inoculations of erysipelas: with a report often original cases, 1893. Clin. Orthop. Relat. 262, 3-11 (1991).
7. Jefford M, Maraskovsky E, Cebon J, Davis ID: The use of dendritic cells in cancer therapy. Lancet Oncol. 2, 343-353 (2001). (Pubitemid 33585939)
8. Steinman RM, Dhodapkar M: Active immunization against cancer with dendritic cells: the near future. Int. J. Cancer 94, 459-473 (2001).
9. Koido S, Hara E, Homma S, Ohkusa T, Gong J, Tajiri H: Cancer immunotherapy by fusions of dendritic cells and tumor cells. Immunotherapy 1(1), 49-62 (2009).
10. Thomas-Kaskel AK, Veelken H: Dendritic-cell vaccination for prostate cancer. Immunotherapy 1(1), 63-72 (2009).
11. Gabrilovich D: Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat. Rev. Immunol. 4(12), 941-952 (2004).
12. Grassi F, Hosmalin A, McIlroy D, Calvez V, Debré P, Autran B: Depletion in blood CD11c-positive dendritic cells from HIV-infected patients. AIDS 13(7), 759-766 (1999). (Pubitemid 29224577)
13. - plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load. Blood 98(8), 2574-2576 (2001).
14. Jones GJ, Watera C, Patterson S et al.: Comparative loss and maturation of peripheral blood dendritic cell subpopulations in African and non-African HIV-1-infected patients. AIDS 15(13), 1657-1663 (2001).
15. + T cells expanded with inactivated-virus-pulsed dendritic cells. J. Virol. 75(19), 8949-8956 (2001).
16. Lu W, Wu X, Lu Y, Guo W, Andrieu JM: Therapeutic dendritic-cell vaccine for simian AIDS. Nat. Med. 9(1), 27-32 (2003).
17. Carbonneil C, Aouba A, Burgard M et al.: Dendritic cells generated in the presence of granulocyte-macrophage colony-stimulating factor and IFN-α are potent inducers of HIV-specific CD8 T cells. AIDS 17(12), 1731-1740 (2003). (Pubitemid 37000091)
18. Almeida M, Cordero M, Almeida J, Orfao A: Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection. AIDS 19(3), 261-271 (2005). (Pubitemid 40396557)
19. Nehete PN, Gambhira R, Nehete BP, Sastry KJ: Dendritic cells enhance detection of antigen-specific cellular immune responses by lymphocytes from rhesus macaques immunized with an HIV envelope peptide cocktail vaccine. J. Med. Primatol. 32(2), 67-73 (2003).
20. WHO, UNAIDS & UNICEF: Towards universal access: scaling up priority HIV/AIDS Interventions in the health sector 1-92. WHO, Geneva, Switzerland (2007).
21. Carr A: HIV protease inhibitor-related lipodystrophy syndrome. Clin. Infect. Dis. 30(Suppl. 2), S135-S142 (2000).
22. Feinberg M: Hidden dangers of incompletely suppressive antiretroviral therapy. Lancet 349, 1408-1409 (1997).
23. Shortman K, Naik SH: Steady-state and inflammatory dendritic-cell development. Nat. Rev. Immunol. 7(1), 19-30 (2007).
24. Steinman RM: Dendritic cells in vivo: a key target for a new vaccine science. Immunity 29, 319-324 (2008).
25. Freudenthal PS, Steinman RM: The distinct surface of human blood dendritic cells as observed after an improved isolation method. Proc. Natl Acad. Sci. USA 87(19), 7698-7702 (1990).
26. Albert ML, Sauter B, Bhardwaj N: Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392(6671), 86-89 (1998). (Pubitemid 28150594)
27. Siegal FP, Kadowaki N, Shodell M et al.: The nature of the principal type 1 interferon-producing cells in human blood. Science 284(5421), 1835-1837 (1999).
28. Marschner A, Rothenfusser S, Hornung V et al.: CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells. Eur. J. Immunol. 35(8), 2347-2357 (2005).
29. Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J: Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19(2), 225-234 (2003). (Pubitemid 37011337)
30. Fonteneau JF, Larsson M, Beignon AS et al.: Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells. J. Virol. 78(10), 5223-5232 (2004). (Pubitemid 38581474)
31. Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ: The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J. Exp. Med. 185(6), 1101-1111 (1997).
32. + T cells: a new role for plasmacytoid dendritic cells in adaptive immunity. Blood 101(9), 3520-3526 (2003).
33. Hoeffel G, Ripoche AC, Matheoud D et al.: Antigen crosspresentation by human plasmacytoid dendritic cells. Immunity 27, 481-492 (2007).
34. Kwon D, Gregorio G, Bitton N, Hendrickson W, Littman D: DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity 16(1), 135-144 (2002).
35. Jiang W, Swiggard WJ, Heufler C: The receptor DEC-205 expressed by dendritic cell and thymic epithelial cells is involved in antigen processing. Nature 375(6527), 151-155 (1995).
36. Granelli-Piperno A, Pritsker A, Pack M et al.: Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction. J. Immunol. 175(7), 4265-4273 (2005). (Pubitemid 41361960)
37. + T cells in a spectrum of human MHC I haplotypes. Proc. Natl Acad. Sci. USA 104(4), 1289-1294 (2007). ■ View to increase the effectiveness of DC vaccine.
38. Schnare M, Barton GM, Holt AC, Takeda K, Akira S, Medzhitov R: Toll-like receptors control activation of adaptive immune responses. Nat. Immunol. 2(10), 947-950 (2001).
39. Medzhitov R: Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1(2), 135-145 (2001).
40. Hornung V, Rothenfusser S, Britsch S et al.: Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168(9), 4531-4537 (2002). (Pubitemid 34441357)
41. Jarrossay D, Napolitani G, Collona M, Sallusto F, Lanzavecchia A : Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur. J. Immunol. 31(11), 3388-3393 (2001).
42. De Gregorio E, D'Oro U, Wack A: Immunology of TLR-independent vaccine adjuvants. Curr. Opin. Immunol. 21(3), 339-345 (2009).
43. Vanbervliet B, Homey B, Durand I et al.: Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces. Eur. J. Immunol. 32(1), 231-242 (2002).
44. McWilliam AS, Nelson D, Thomas JA, Holt PG: Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J. Exp. Med. 179(4), 1331-1336 (1994).
45. Faure-André G, Vargas P, Yuseff MI et al.: Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain. Science 322(5908), 1705-1710 (2008).
46. Iwasaki A, Medzhitov R: Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5(10), 987-995 (2004). ■■ First clinical report showing the impact of vaccine on viral load in HIV infection.
47. Kalinski P, Hilkens CMU, Wierenga EA, Kapsenberg ML: T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol. Today 20(12), 561-567 (1999).
48. Nakano H, Lin KL, Yanagita M et al.: Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses. Nat. Immunol. 10(4), 394-402 (2009).
49. Romani N, Gruner S, Brang D et al.: Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180(1), 83-93 (1994).
50. Sallusto F, Lanzavecchia A: Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α. J. Exp. Med. 179(4), 1109-1118 (1994).
51. Jonuleit H, Kühn U, Müller G et al.: Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol. 27(12), 3135-3142 (1997).
52. Weissman D, Ni H, Scales D et al.: HIV-Gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response. J. Immunol. 165, 4710-4717 (2000). (Pubitemid 30795854)
53. Lu W, Arraes LC, Ferreira WT, Andrieu JM: Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat. Med. 10, 1359-1365 (2004).
54. Allard SD, Pletinckx K, Breckpot K et al..: Functional T-cell responses generated by dendritic-cells expressing the early HIV-1 proteins Tat, Rev and Nef. Vaccine 26(29-30), 3735-3741 (2008).
55. Ahlers JD, Belyakov IM: Strategies for recruiting and targeting dendritic cells for optimizing HIV vaccines. Trends Mol. Med. 15(6), 263-274 (2009).
56. high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients. Blood 108(8), 2655-2661 (2006).
57. Jacobs B, Wuttke M, Papewalis C et al.: Characterization of monocyte-derived IFN-α-generated dendritic cells. Horm. Metab. Res. 40(2), 117-121 (2008).
58. Tawab A, Fan Y, Read EJ, Kurlander RJ: Effect of ex vivo culture duration on phenotype and cytokine production by mature dendritic cells derived from peripheral blood monocytes. Transfusion 49(3), 536-547 (2009).
59. Landi A, Babiuk LA, van Drunen Littel-van den Hurk S: High transfection efficiency, gene expression, and viability of monocyte-derived human dendritic cells after nonviral gene transfer. J. Leukoc. Biol. 82(4), 849-860 (2007).
60. Sapp M, Engelmayer J, Larsson M, Granelli-Piperno A, Steinman R, Bhardwaj N: Dendritic cells generated from blood monocytes of HIV-1 patients are not infected and act as competent antigen presenting cells eliciting potent T-cell responses. Immunol. Lett. 66(1-3), 121-128 (1999).
61. Chougnet C, Cohen SS, Kawamura T et al.: Normal immune function of monocyte-derived dendritic cells from HIV-infected individuals: implications for immunotherapy. J. Immunol. 163(3), 1666-1673 (1999). (Pubitemid 29352792)
62. Buisson S, Benlahrech A, Gazzard B, Gotch F, Kelleher P, Patterson S: Monocyte-derived dendritic cells from HIV type 1-infected individuals show reduced ability to stimulate T cells and have altered production of interleukin (IL)-12 and IL-10. J. Infect. Dis. 199(12), 1862-1871 (2009)
63. Reis e Sousa C: Dendritic cells in a mature age. Nat. Rev. 6, 476-483 (2006).
64. + regulatory T cells. J. Dermatol. Sci. 54(2), 69-75 (2009).
65. + regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood 104(10), 3249-3256 (2004). (Pubitemid 39507143)
66. Nilsson J, Boasso A, Velilla PA et al.: HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood 108(12), 3808-3817 (2006). (Pubitemid 44864563)
67. + regulatory T cells from HIV-infected individuals. Proc. Natl Acad. Sci. USA 104(9), 3390-3395 (2007).
68. Eggena MP, Barugahare B, Jones N et al.: Depletion of regulatory T cells in HIV infection is associated with immune activation. J. Immunol. 174(7), 4407-4414 (2005). (Pubitemid 40396024)
69. + regulatory T cells. J. Infect. Dis. 199(9), 1318-1322 (2009).
70. Holmes D, Jiang Q, Zhang L, Su L: Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis. Immunol. Res. 41(3), 248-266 (2008).
71. -CD25 T cells expressing FoxP3 in IL-2-treated HIV-infected patients. J. Clin. Invest. 115(7), 1839-1847 (2005).
72. Ziegler SF: FoxP3: not just for regulatory T cells anymore. Eur. J. Immunol. 37(1), 21-23 (2007).
73. + regulatory T cells allows for their purification from expansion cultures. Blood 113(21), 5125-5133 (2009).
74. Loussert-Ajaka I, Chaix ML, Korber B et al.: Variability of human immunodeficiency virus type 1 group O strains isolated from Cameroonian patients living in France. J. Virol. 69(9), 5640-5649 (1995).
75. Korber B, Muldoon M, Theiler J et al.: Timing the ancestor of the HIV-1 pandemic strains. Science 288(5472), 1789-1796 (2000). (Pubitemid 30399011)
76. Taylor BS, Hammer SM: The challenge of HIV-1 subtype diversity. N. Engl. J. Med. 359(18), 1965-1966 (2008).
77. Malim MH, Emerman M: HIV-1 sequence variation: drift, shift, and attenuation. Cell 104(4), 469-472 (2001).
78. Garcia F, Lejeune M, Climent N et al.: Therapeutic immunization with dendritic cells loaded with heat-inactivated autologous HIV-1 in patients with chronic HIV-1 infection. J. Infect. Dis. 191, 1680-1685 (2005).
79. Altfeld M, Addo MM, Shankarappa R et al.: Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequence. J. Virol. 77(13), 7330-7340 (2003). (Pubitemid 36734501)
80. Fischer W, Perkins S, Theiler J et al.: Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat. Med. 13(1), 100-106 (2007).
81. Frahm N, Kaufmann DE, Yusim K et al.: Increased sequence diversity coverage improves detection of HIV-specific T cell responses. J. Immunol. 179(10), 6638-6650 (2007).
82. Rossio JL, Esser MT, Suryanarayana K et al.: Inactivation of human immunodeficiency virus type I infectivity with preservation of conformational and functional integrity of virion surface proteins. J. Virol. 72, 7992-8001 (1998). (Pubitemid 28421792)
83. Larsson M, Wilkens DT, Fonteneau JF et al.: Amplification of low-frequency antiviral CD8 T cell responses using autologous dendritic cells. AIDS 16, 171-180 (2002). (Pubitemid 34118563)
84. Connolly NC, Whiteside TL, Wilson C, Kondragunta V, Rinaldo CR, Riddler SA: Therapeutic immunization with human immunodeficiency virus type 1 (HIV-1) peptide-loaded dendritic cells is safe and induces immunogenicity in HIV-1-infected individuals. Clin. Vac. Immunol. 15(2), 284-292 (2008). ■ Clinical trial using vaccine made of DCs pulsed with viral peptides.
85. Van Gulck ERA, Ponsaerts P, Heyndrickx L et al.: Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins. Blood 107(5), 1818-1827 (2006).
86. + T cells by dendritic cells transfected with mRNA encoding cytoplasm- or lysossome-targeted Nef. Blood 107(5), 1963-1969 (2006).
87. Van Gulck ER, Vanham G, Heyndrickx L et al.: Efficient in vitro expansion of human immunodeficiency virus (HIV)-specific T-cell responses by gag mRNA-electroporated dendritic cells from treated and untreated HIV type 1-infected individuals. J. Virol. 82(7), 3561-3573 (2008).
88. + T-cell responses from chronically infected individuals. J. Virol. 75(5), 2142-2153 (2000).
89. + T cells by cross-presentation of DCs. J. Virol. 77(19), 10250-10259 (2003). (Pubitemid 37129668)
90. Albert ML: Death-defying immunity: do apoptotic cells influence antigen processing and presentation? Nat. Rev. Immunol. 4(3), 223-231 (2004).
91. + T lymphocytes. Proc. Natl Acad. Sci. USA 101(16), 6092-6097 (2004).
92. Heyward WL, MacQueen KM, Goldenthal KL: HIV vaccine development and evaluation: realistic expectations. AIDS Res. Hum. Retrovir. (Suppl. 3) S205-S210 (1998).
93. Kundu SK, Engleman E, Benike C et al.: A pilot clinical trial of HIV antigen-pulsed allogeneic and autologous dendritic cell therapy in HIV infected patients. AIDS Res. Hum. Retrovir. 14, 551-560 (1998).
94. Shapero MH, Kundu SK, Engleman E, Laus R, van Schooten WC, Merigan TC: In vivo persistence of donor cells following adoptive transfer of allogeneic dendritic cells in HIV-infected patients. Cell Transplant 9(3), 307-317 (2000).
95. Ide F, Nakamura T, Tomizawa M et al.: Peptide-loaded dendritic-cell vaccination followed by treatment interruption for chronic HIV-1 infection: a Phase 1 trial. J. Med. Virol. 78(6), 711-718 (2006).
96. Gandhi RT, O'Neill D, Bosch RJ et al.: A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy. Vaccine doi:10.1016/j. vaccine.2009.05.016 (2009).
97. Caux C, Dezutter-Dambuyant D, Banchereau J: GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells. Nature 360, 258-261 (1992).
98. Nestle FO, Banchereau J, Hart D: Dendritic cells: On the move from bench to bedside. Nat. Med. 7(7), 761-765 (2001). ■■ Discusses various aspects of standardization in the protocols of DC-based vaccine.
99. Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ: Dendritic cell immunotherapy: mapping the way. Nat. Med. 10(5), 475-480 (2004). ■■ Focuses on the difficulties and discusses aspects of standardization in clinical trials using DCs.
100. 111In-oxine used as a therapeutic vaccine in HIV-1-infected patients. Immunotherapy 1(3), 347-354 (2009).
101. Alvarez D, Vollmann EH, von Andrian UH: Mechanisms and consequences of dendritic cell migration. Immunity 29(3), 325-342 (2008).
102. De Vries IJ, Krooshoop DJ, Scharenborg NM et al.: Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res. 63(1), 12-17 (2003).
103. + regulatory T cells. Proc. Natl Acad. Sci. USA 104(8), 2821-2826 (2007).
104. Belkaid Y, Oldenhove G: Tuning microenvironments: induction of regulatory T cells by dendritic cells. Immunity 29(3), 362-371 (2008).
105. Barratt-Boyes SM, Zimmer MI, Harshyne LA et al.: Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J. Immunol. 164(5), 2487-2495 (2000).
106. Thomas R, Chambers M, Boytar R et al.: Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy. Melanoma Res. 9, 474-481 (1999). (Pubitemid 29494113)
107. + T-cell in humans without foreign helper epitopes. J. Clin. Invest. 105(6), R9-R14 (2000).
108. Serody JS, Collins EJ, Tisch RM, Kuhns JJ, Frelinger JA: T cell activity after dendritic cell vaccination is dependent on both the type of antigen and the mode of delivery. J. Immunol. 164, 4961-4967 (2000).
109. De Rosa SC, Lu FX, Yu J et al.: Vaccination in humans generates broad T cell cytokine responses. J. Immunol. 173(9), 5372-5380 (2004). (Pubitemid 39392120)
110. Makedonas G, Betts MR: Polyfunctional analysis of human T cell responses: importance in vaccine immunogenicity and natural infection. Springer Semin. Immunopathol. 28(3), 209-219 (2006). ■■ Reports the presence of multiple cytokine-producing lymphocytes in response to infection and immunization.
111. + T cells. Blood 107(12), 4781-4789 (2006).
112. Brenchley JM, Price DA, Schacker TW et al.: Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12(12), 1365-1371 (2006). ■■ Evidence of the role of microbial translocation as vital in HIV infection.
113. Ludewig B, Ochsenbein AF, Odermatt B, Paulin D, Hengartner H, Zinkernagel RM: Immunotherapy with dendritic cells directed against tumor antigens shared with normal host T cells results in severe autoimmune disease. J. Exp. Med. 191, 795-803 (2000).
114. Clinicaltrials.gov. A service of the U.S. National Institutes of Health www.clinicaltrials.gov