Local and systemic effects of intranodally injected CpG-C immunostimulatory-oligodeoxyribonucleotides in macaques

Journal of Immunology

Volumn 177, Issue 12, 2006, Pages 8531-8541

  Teleshova, Natalia ^a,f   Kenney, Jessica ^a   Van Nest, Gary ^b   Marshall, Jason ^b   Lifson, Jeffrey D ^c   Sivin, Irving ^a   Dufour, Jason ^d   Bohm, Rudolf ^d   Gettie, Agegnehu ^e   Robbiani, Melissa ^a  

^a POPULATION COUNCIL   (United States)

^b Dynavax Technologies Corporation   (United States)

^c SAIC FREDERICK INC   (United States)

^d TULANE NATIONAL PRIMATE RESEARCH CENTER   (United States)

^e AARON DIAMOND AIDS RESEARCH CENTER   (United States)

^f MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; B7 ANTIGEN; CD123 ANTIGEN; CD86 ANTIGEN; CHEMOKINE; CPG C OLIGODEOXYRIBONUCLEOTIDE C274; CYTOKINE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; INTERLEUKIN 12; INTERLEUKIN 3; INTERLEUKIN 6; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MONOCYTE CHEMOTACTIC PROTEIN 1; OLIGODEOXYRIBONUCLEOTIDE; RANTES; TUMOR NECROSIS FACTOR ALPHA; VIRUS ANTIGEN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DENDRITIC CELL; DRUG EFFECT; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; IMMUNOGENICITY; IMMUNOPHENOTYPING; IN VITRO STUDY; IN VIVO STUDY; LYMPH NODE; LYMPHOCYTE COUNT; MACACA; MALE; NONHUMAN; PLASMA CELL; PRIORITY JOURNAL; RETROVIRUS INFECTION; SIMIAN IMMUNODEFICIENCY VIRUS;

EID: 33845455695     PISSN: 00221767     EISSN: None     Source Type: Journal    
DOI: 10.4049/jimmunol.177.12.8531     Document Type: Article

References (106)

1. Pulendran, B. 2004. Modulating vaccine responses with dendritic cells and Toll-like receptors. Immunol. Rev. 199: 227-250.
2. Iwasaki, A., and R. Medzhitov. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5: 987-995.
3. Colonna, M., G. Trinchieri, and Y. I. Liu. 2004. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5: 1219-1226.
4. McKenna, K., A. S. Beignon, and N. Bhardwaj. 2005. Plasmacytoid dendritic cells: linking innate and adaptive immunity. J. Virol. 79: 17-27.
5. Fayette, J., B. Dubois, S. Vandenabelle, J.-M. Bridon, B. Vanbervliet, I. Durand, J. Banchereau, C. Caux, and F. Briere. 1997. Human dendritic cells skew isotype switching of CD40-activated naive B cells towards IgA1 and IgA2. J. Exp. Med. 185: 1909-1918.
6. MacLennan, I., and C. Vinuesa. 2002. Dendritic cells, BAFF, and APRIL: innate players in adaptive antibody responses. Immunity 17: 235-238.
7. Le Bon, A., G. Schiavoni, G. D'Agostino, I. Gresser, F. Belardelli, and D. F. Tough. 2001. Type 1 interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14: 461-470.
8. Colino, J., Y. Shen, and C. M. Snapper. 2002. Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide- specific immunoglobulin isotype responses in vivo through distinct mechanisms. J. Exp. Med. 195: 1-13.
9. Jego, G., V. Pascual, A. K. Palucka, and J. Banchereau. 2005. Dendritic cells control B cell growth and differentiation. Curr. Dir. Autoimmun. 8: 124-139.
10. Balazs, M., F. Martin, T. Zhou, and I. Kearney. 2002. Blood dendritic cells interact with splenic marginal zone B cells to initiate T-independent immune responses. Immunity 17: 341-352.
11. Litinskiy, M. B., B. Nardelli, D. M. Hilbert, B. He, A. Schaffer, P. Casali, and A. Cerutti. 2002. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat. Immunol. 3: 822-829.
12. Jego, G., A. K. Palucka, J.-P. Blanck, C. Chalouni, V. Pascual, and J. Banchereau. 2003. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19: 225-234.
13. Desrosiers, R. C. 1990. The simian immunodeficiency viruses. Annu. Rev. Immunol. 8: 557-578.
14. Coates, P. T., S. M. Barratt-Boyes, L. Zhang, V. S. Donnenberg, P. I. O'Connell, A. J. Logar, F. J. Duncan, M. Murphey-Corb, A. D. Donnenberg, A. E. Morelli, et al. 2003. Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand. Blood 102: 2513-2521.
15. Pichyangkul, S., T. P. Endy, S. Kalayanarooj, A. Nisalak, K. Yongvanitchit, S. Green, A. L. Rothman, F. A. Ennis, and D. H. Libraty. 2003. A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity. J. Immunol. 171: 5571-5578.
16. Teleshova, N., J. Jones, J. Kenney, J. Purcell, R. Bohm, A. Gettie, and M. Pope. 2004. Short-term Flt3L treatment effectively mobilizes macaque myeloid dendritic cells. J. Leukocyte Biol. 75: 1102-1110.
17. Teleshova, N., J. Kenney, J. Jones, J. Marshall, G. Van Nest, J. Dufour, R. Bohm, J. D. Lifson, A. Gettie, and M. Pope. 2004. CpG-C immunostimulatory oligodeoxyribonucleotide activation of plasmacytoid dendritic cells in rhesus macaques to augment the activation of IFN-γ-secreting simian immunodeficiency virus-specific T cells. J. Immunol. 173: 1647-1657.
18. Frank, I., and M. Pope. 2002. The enigma of dendritic cell-immunodeficiency virus interplay. Curr. Mol. Med. 2: 229-248.
19. Teleshova, N., I. Frank, and M. Pope. 2003. Immunodeficiency virus exploitation of dendritic cells m the early steps of infection. J. Leukocyte Biol. 74: 683-690.
20. Fonteneau, J. F., M. Larsson, A. S. Beignon, K. McKenna, I. Dasilva, A. Amara, Y. J. Liu, J. D. Lifson, D. R. Littman, and N. Bhardwaj. 2004. Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells. J. Virol. 78: 5223-5232.
21. Mehlhop, E. R., L. A. Villamide, I. Frank, A. Gettie, C. Santisteban, D. Messmer, R. Ignatius, J. D. Lifson, and M, Pope. 2002. Enhanced in vitro stimulation of rhesus macaque dendritic cells for activation of SIV-specific T cell responses. J. Immunol. Methods 260: 219-234.
22. + T cell responses. AIDS 34: 7-19.
23. Larsson, M., J. F. Fonteneau, M. Lirvall, P. Haslett, J. D. Lifson, and N. Bhardwaj. 2002. Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus. AIDS 16: 1319-1329.
24. Granelli-Piperno, A., A. Golebiowska, C. Trumpfheller, F. P. Siegal, and R. M. Steinman. 2004. HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation. Proc. Natl. Acad. Sci. USA 101: 7669-7674.
25. Vachot, L., S. G. Turville, S. Trapp, S. Peretti, G. Morrow, I. Frank, and M. Pope. 2006. Sleeping with the enemy: the insidious relationship between dendritic cells and immunodeficiency viruses. In Handbook of Dendritic Cells. M. B. Lutz, N. Romani, and A. Steinkasserer, eds. Wiley-VCH, Weinheim, Germany, pp. 773-797.
26. Turville, S. G., S. Peretti, and M. Pope. 2006. Lymphocyte-dendritic cell interactions and mucosal acquisition of SIV/HIV infection. Curr. Opin. HIV AIDS 1: 3-9.
27. - plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load. Blood 98: 2574-2576.
28. Soumelis, V., I. Scott, F. Gheyas, D. Bouhour, G. Cozon, L. Cotte, L. Huang, J. A. Levy, and Y. J. Liu. 2001. Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. Blood 98: 906-912.
29. Soumelis, V., I. Scott, Y.-J. Liu, and J. Levy. 2002. Natural interferon-α producing cells in HIV infection. Hum. Immunol. 63: 1206-1212.
30. Macatonia, S. E., R. Lau, S. Patterson, A. J. Pinching, and S. C. Knight. 1990. Dendritic cell infection, depletion and dysfunction in HIV infected individuals. Immunology 71: 38-45.
31. + (myeloid) dendritic cell numbers in primary HIV-1 infection. Blood 98: 3016-3021.
32. + dendritic cells with reduced CD80 and CD86 expression in lymphoid tissue during acute HIV-1 infection. AIDS 16: 683-692.
33. + dendritic cells in lymph nodes during SIV infection of macaques. J. Med. Primatol. 33: 16-24.
34. Choi, Y. K., B. A. Fallert, M. A. Murphey-Corb, and T. A. Reinhart. 2003. Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo. Blood 101: 1684-1691.
35. Lane, H. C., H. Masur, L. C. Edgar, G. Whalen, A. H. Rook, and A. S. Fauci. 1983. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 309: 453-458.
36. Pahwa, S. G., M. T. Quilop, M. Lange, R. N. Pahwa, and M. H. Grieco. 1984. Defective B-lymphocyte function in homosexual men in relation to the acquired immunodeficiency syndrome. Ann. Intern. Med. 101: 757-763.
37. Katz, I. R., S. E. Krown, B. Safai, H. F. Oettgen, and M. K. Hoffmann. 1986. Antigen-specific and polyclonal B-cell responses in patients with acquired immunodeficiency disease syndrome. Clin. Immunol. Immunopathol. 39: 359-367.
38. Gaidano, G., D. Capello, and A. Carbone. 2000. The molecular basis of acquired immunodeficiency syndrome-related lymphomagenesis. Semin. Oncol. 27: 431-441.
39. Amadori, A., A. De Rossi, G. P. Faulkner-Valle, and L. Chieco-Bianchi. 1988. Spontaneous in vitro production of virus-specific antibody by lymphocytes from HIV-infected subjects. Clin. Immunol. Immunopathol. 46: 342-351.
40. Martinez-Maza, O., E. Crabb, R. T. Mitsuyasu, J. L. Fahey, and J. V. Giorgi. 1987. Infection with the human immunodeficiency virus (HIV) is associated with an in vivo increase in B lymphocyte activation and immaturity. J. Immunol. 138: 3720-3724.
41. Moir, S., A. Malaspina, K. M. Ogwaro, E. T. Donoghue, C. W. Hallahan, L. A. Ehler, S. Liu, J. Adelsberger, R. Lapointe, P. Hwu, et al. 2001. HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals. Proc. Natl. Acad. Sci. USA 98: 10362-10367.
42. Fournier, A. M., J. M. Fondere, C. Alix-Panabieres, C. Merle, V. Baillat, M. F. Huguet, J. Taib, V. Ohayon, M. Zembala, J. Reynes, and J. P. Vendrell. 2002. Spontaneous secretion of immunoglobulins and anti-HIV-1 antibodies by in vivo activated B lymphocytes from HIV-1-infected subjects: monocyte and natural killer cell requirement for in vitro terminal differentiation into plasma cells. Clin. Immunol. 103: 98-109.
43. Shirai, A., M. Cosentino, S. F. Leitman-Klinman, and D. M. Klinman. 1992. Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. J. Clin. Invest. 89: 561-566.
44. Ammann, A. J., G. Schiffman, D. Abrams, P. Volberding, J. Ziegler, and M. Conant. 1984. B-cell immunodeficiency in acquired immune deficiency syndrome. J. Am. Med. Assoc, 251: 1447-1449.
45. Marshall, J. D., K. Fearon, C. Abbate, S. Subramanian, P. Yee, J. Gregorio, R. L. Coffman, and G. Van Nest. 2003. Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions. J. Leukocyte Biol. 73: 781-792.
46. Hartmann, G., J. Battiany, H. Poeck, M. Wagner, M. Kerkmann, N. Lubenow, S. Rothenfusser, and S. Endres. 2003. Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-α induction in plasmacytoid dendritic cells. Eur. J. Immunol. 33: 1633-1641.
47. Poeck, H., M. Wagner, J. Battiany, S. Rothenfusser, D. Wellisch, V. Hornung, B. Jahrsdorfer, T. Giese, S. Endres, and G. Hartmann. 2004. Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help. Blood 103: 3058-3064.
48. Klinman, D. M. 2004. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat. Rev. Immunol. 4: 249-258.
49. Hartmann, G., R. D. Weeratna, Z. K. Ballas, P. Payette, S. Blackwell, I. Suparto, W. L. Rassmussen, M. Waldschmidt, D. Sajuthi, R. H. Purcell, et al. 2000. Delineation of a CpG phosphorothionate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo. J. Immunol. 164: 1617-1624.
50. Verthelyi, D., V. W. Wang, J. D. Lifson, and D. M. Klinman. 2004. CpG oligodeoxynucleotides improve the response to hepatitis B immunization in healthy and SIV-infected rhesus macaques. AIDS 18: 1003-1008.
51. Klinman, D. M., D. Currie, I. Gursel, and D. Verthelyi. 2004. Use of CpG oligodeoxynucleotides as immune adjuvants. Immunol. Rev. 199: 201-216.
52. Klinman, D. M., H. Xie, S. F. Little, D. Currie, and B. E. Ivins. 2004. CpG oligonucleotides improve the protective immune response induced by the anthrax vaccination of rhesus macaques. Vaccine 22: 2881-2886.
53. Verthelyi, D., M. Gursel, R. T. Kenney, J. D. Lifson, S. Liu, J. Mican, and D. M. Klinman. 2003. CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection. J. Immunol. 170: 4717-4723.
54. Ahmed, R. K., G. Biberfeld, and R. Thorstensson. 2005. Innate immunity in experimental SIV infection and vaccination. Mol. Immunol. 42: 251-258.
55. + T cell responses to protein antigens in rhesus macaques in vivo. Vaccine 23: 3310-3317.
56. Marshall, J. D., K. L. Fearon, D. Higgins, E. M. Hessel, H. Kanzler, C. Abbate, P. Yee, J. Gregorio, T. D. Cruz, J. O. Lizcano, et al. 2005. Superior activity of the type C class of ISS in vitro and in vivo across multiple species. DNA Cell Biol. 24: 63-72.
57. Teleshova, N., J. Kenney, G. Van Nest, J. Marshall, J. D. Lifson, I. Sivin, J. Dufour, R. Bohm, A. Gettie, and M. Pope. 2006. CpG-C ISS-ODN activation of blood-derived B cells from healthy and chronic immunodeficiency virus-infected macaques. J. Leukocyte Biol. 79: 257-267.
58. Abel, K., Y. Wang, L. Fritts, E. Sanchez, E. Chung, P. Fitzgerald-Bocarsly, A. M. Krieg, and C. J. Miller. 2005. Deoxycytidyl- deoxyguanosine oligonucleotide classes A, B, and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear cells and distinct α interferon responses in TLR9-expressing rhesus monkey plasmacytoid dendritic cells. Clin. Diagn. Lab. Immunol. 12: 606-621.
59. Heikenwalder, M., M. Polymenidou, T. Junt, C. Sigurdson, H. Wagner, S. Akira, R. Zinkernagel, and A. Aguzzi. 2004. Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat. Med. 10: 187-192.
60. Schmidt, U., H. Wagner, and T. Miethke. 1999. CpG-DNA upregulates the major acute-phase proteins SAA and SAP. Cell Microbiol. 1: 61-67.
61. von Beust, B. R., P. Johansen, K. A. Smith, A. Bot, T. Storni, and T. M. Kundig. 2005. Improving the therapeutic index of CpG oligodeoxynucleotides by intralymphatic administration. Eur. J. Immunol. 35: 1869-1876.
62. Harouse, J. M., A. Gettie, R. C. Tan, J. Blanchard, and C. Cheng-Mayer. 1999. Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs. Science 284: 816-819.
63. Tan, R. C., J. M. Harouse, A. Gettie, and C. Cheng-Mayer. 1999. In vivo adaptation of SHIV(SF162): chimeric virus expressing a NSI, CCRS-specific envelope protein. J. Med. Primatol. 28: 164-168.
64. Harouse, J. M., A. Gettie, T. Eshetu, R. C. Tan, R. Bohm, J. Blanchard, G. Baskin, and C. Cheng-Mayer. 2001. Mucosal transmission and induction of simian AIDS by CCR5-specific simian/human immunodeficiency virus SHIV(SF162P3). J. Virol. 75: 1990-1995.
65. Parren, P. W., P. A. Marx, A. J. Hessell, A. Luckay, J. Harouse, C. Cheng-Mayer, J. P. Moore, and D. R. Burton. 2001. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J. Virol. 75: 8340-8347.
66. Hsu, M., J. M. Harouse, A. Gettie, C. Buckner, J. Blanchard, and C. Cheng-Mayer. 2003. Increased mucosal transmission but not enhanced pathogenicity of the CCR5-tropic, simian AIDS-inducing simian/human immunodeficiency virus SHIV(SF162P3) maps to envelope gp120. J. Virol. 77: 989-998.
67. Animal Welfare Information Center. 2001. Title 9, Chapter 1, Subchapter A: Animals and Animal Products. In Code of Federal Regulations: Animal Welfare Act and Regulation. US Department of Agriculture, Beltsville, MD.
68. Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources. 1985. Guide for the Care and Use of Laboratory Animals. US Department of Health and Human Services. National Institutes of Health, Bethesda, MD. pp. 1-83.
69. Hu, J., M. Pope, U. O'Doherty, C. Brown, and C. J. Miller. 1998. Immunophenotypic characterization of SIV-infected cells in cervix, vagina and draining lymph nodes of chronically infected rhesus macaques. Lab. Invest. 78: 435-451.
70. Hu, J., C. J. Miller, U. O'Doherty, P. A. Marx, and M. Pope. 1999. The dendritic cell-T cell milieu of the lymphoid tissue of the tonsil provides a locale in which SIV can reside and propagate at chronic stages of infection. AIDS Res. Hum. Retroviruses 15: 1305-1314.
71. Chertova, E., J. W. Bess, Jr., B. J. Crise, I. R. Sowder, T. M. Schaden, J. M. Hilburn, J. A. Hoxie, R. E. Benveniste, J. D. Lifson, L. E. Henderson, and L. O. Arthur. 2002. Envelope glycoprotein incorporation, not shedding of surface envelope glycoprotein (gp120/SU), is the primary determinant of SU content of purified human immunodeficiency virus type 1 and simian immunodeficiency virus. J. Virol. 76: 5315-5325.
72. Bess, J. W., Jr., R. J. Gorelick, W. J. Bosche, L. E. Henderson, and L. O. Arthur. 1997. Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations. Virology 230: 134-144.
73. + lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment. J. Virol. 75: 10187-10199.
74. Belyakov, I. M., and J. A. Berzofsky. 2004. Immunobiology of mucosal HIV infection and the basis for development of a new generation of mucosal AIDS vaccines. Immunity 20: 247-253.
75. Pantaleo, G., and R. A. Koup. 2004. Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know. Nat. Med. 10: 806-810.
76. Goulder, P. J., and D. I. Watkins. 2004. HIV and SIV CTL escape: implications for vaccine design. Nat. Rev. Immunol. 4: 630-640.
77. Letvin, N. L. 2005. Progress toward an HIV vacine. Annu. Rev. Med. 56: 213-223.
78. He, B., X. Qiao, and A. Cerutti. 2004. CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10. J. Immunol. 173: 4479-4491.
79. Krieg, A. M. 2002. CpG motifs in bacterial DNA and their immune effects. Annu. Rev. Immunol. 20: 709-760.
80. Cafaro, A., F. Titti, C. Fracasso, M. T. Maggiorella, S. Baroncelli, A. Caputo, D. Goletti, A. Borsetti, M. Pace, E. Fanales-Belasio, et al. 2001. Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P). Vaccine 19: 2862-2877.
81. Wang, Y., K. Abel, K. Lantz, A. M. Krieg, M. B. McChesney, and C. J. Miller. 2005. The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the TLR9 agonist, CpG ODN, induce antiviral cytokines and chemokines but do not prevent vaginal transmission of simian immunodeficiency virus when applied intravaginally to rhesus macaques. J. Virol. 79: 14355-14370.
82. Wille-Reece, U., B. J. Flynn, K. Lore, R. A. Koup, A. P. Miles, A. Saul, R. M. Kedl, J. J. Mattapallil, W. R. Weiss, M. Roederer, and R. A. Seder. 2006. Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J. Exp. Med. 203: 1249-1258.
83. Patterson, S., A. Rae, N. Hockey, J. Gilmour, and F. Gotch. 2001. Plasmacytoid dendritic cells are highly susceptible to human immunodeficiency virus type 1 infection and release infectious virus. J. Virol. 75: 6710-6713.
84. Yonezawa, A., R. Morita, A. Takaori-Kondo, N. Kadowaki, T. Kitawaki, T. Hori, and T. Uchiyama. 2003. Natural α interferon-producing cells respond to human immunodeficiency virus type 1 with α interferon production and maturation into dendritic cells. J. Virol. 77: 3777-3784.
85. Grassi, F., A. Hosmalin, D. McIlroy, V. Calvez, P. Debre, and B. Autran. 1999. Depletion in blood CD11c-positive dendritic cells from HIV-infected patients. AIDS 13: 759-766.
86. Chehimi, J., D. E. Campbell, L. Azzoni, D. Bacheller, E. Papasavvas, G. Jerandi, K. Mounzer, J. Kostman, G. Trinchieri, and L. J. Montaner. 2002. Persistent decreases in blood plasmacytoid dendritic cell number and function despite effective highly active antiretroviral therapy and increased blood myeloid dendritic cells in HIV-infected individuals. J. Immunol. 168: 4796-4801.
87. Yoneyama, H., K. Matsuno, Y. Zhang, T. Nishiwaki, M. Kitabatake, S. Ueha, S. Narumi, S. Morikawa, T. Ezaki, B. Lu, et al. 2004. Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules. Int. Immunol. 16: 915-928.
88. Vanbervliet, B., N. Bendriss-Vermare, C. Massacrier, B. Homey, O. de Bouteiller, F. Briere, G. Trinchieri, and C. Caux. 2003. The inducible CXCR3 ligands control plasmacytoid dendritic cell responsiveness to the constitutive chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12. J. Exp. Med. 198: 823-830.
89. Davila, E., M. G. Velez, C. J. Heppelmann, and E. Celis. 2002. Creating space: an antigen-independent, CpG-induced peripheral expansion of naive and memory T lymphocytes in a full T-cell compartment. Blood 100: 2537-2545.
90. Gibson, S. J., J. M. Lindh, T. R. Riter, R. M. Gleason, L. M. Rogers, A. E. Fuller, J. L. Oesterich, K. B. Gorden, X. Qiu, S. W. McKane, et al. 2002. Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod. Cell Immunol. 218: 74-86.
91. Hirano, T. 1998. Interleukin 6 and its receptor: ten years later. Int. Rev. Immunol. 16: 249-284.
92. Kimata, H., A. Yoshida, C. Ishioka, M. Fujimoto, I. Lindley, and K. Furusho. 1996. RANTES and macrophage inflammatory protein 1 α selectively enhance immunoglobulin (IgE) and IgG4 production by human B cells. J. Exp. Med. 183: 2397-2402.
93. Sims-Mourtada, J. C., L. Guzman-Rojas, R. Rangel, D. X. Nghiem, S. E. Ullrich, C. Guret, K. Cain, and H. Martinez-Valdez. 2003. In vivo expression of interleukin-8, and regulated on activation, normal, T-cell expressed, and secreted, by human germinal centre B lymphocytes. Immunology 110: 296-303.
94. Tangye, S. G., and P. D. Hodgkin. 2004. Divide and conquer the importance of cell division in regulating B-cell responses. Immunology 112: 509-520.
95. Corcione, A., G. Tortolina, R. Bonecchi, N. Battilana, G. Taborelli, F. Malavasi, S. Sozzani, L. Ottonello, F. Dallegri, and V. Pistoia. 2002. Chemotaxis of human tonsil B lymphocytes to CC chemokine receptor (CCR) 1, CCR2 and CCR4 ligands is restricted to non-germinal center cells. Int. Immunol. 14: 883-892.
96. Ashkar, A. A., and K. L. Rosenthal. 2002. Toll-like receptor 9, CpG DNA and innate immunity. Curr. Mol. Med. 2: 545-556.
97. Krieg, A. M., S. M. Efler, M. Wittpoth, M. J. Al Adhami, and H. L. Davis. 2004. Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. J. Immunother. 27: 460-471.
98. Proudfoot, A. E. 2002. Chemokine receptors: multifaceted therapeutic targets. Nat. Rev. Immunol. 2: 106-115.
99. Lusso, P. 2002. HIV and chemokines: implications for therapy and vaccine. Vaccine 20: 1964-1967.
100. Lehner, T. 2002. The role of CCR5 chemokine ligands and antibodies to CCR5 coreceptors in preventing HIV infection. Trends Immunol. 23: 347-351.
101. Ballas, Z. K., W. L. Rasmussen, and A. M. Krieg. 1996. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J. Immunol. 157: 1840-1845.
102. Verthelyi, D., and D. M. Klinman. 2003. Immunoregulatory activity of CpG oligonucleotides in humans and nonhuman primates, Clin. Immunol. 109: 64-71.
103. Siegal, F. P., C. Lopez, P. A. Fitzgerald, K. Shah, P. Baron, I. Z. Leiderman, D. Imperato, and S. Landesman. 1986. Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity. J. Clin. Invest. 78: 115-123.
104. Siegal, F. P., P. Fitzgerald-Bocarsly, B. K. Holland, and M. Shodell. 2001. Interferon-α generation and immune reconstitution during antiretroviral therapy for human immunodeficiency virus infection. AIDS 15: 1603-1612.
105. Lopez, C., P. A. Fitzgerald, and F. P. Siegal. 1983. Severe acquired immune deficiency syndrome in male homosexuals: diminished capacity to make interferon-α in vitro associated with severe opportunistic infections. J. Infect. Dis. 148: 962-966.
106. Marshall, J. D., J. Chehimi, G. Gri, J. R. Kostman, L. J. Montaner, and G. Trinchieri. 1999. The interleukin-12-mediated pathway of immune events is dysfunctional in human immunodeficiency virus-infected individuals. Blood 94: 1003-1011.