Herpes simplex virus antigens directly activate NK cells via TLR2, thus facilitating their presentation to CD4 T lymphocytes

Journal of Immunology

Volumn 188, Issue 9, 2012, Pages 4158-4170

  Kim, Min ^a,b   Osborne, Naomi R ^a,b   Zeng, Weiguang ^c   Donaghy, Heather ^a   McKinnon, Kay ^d   Jackson, David C ^c   Cunningham, Anthony L ^a,b  

^a WESTMEAD HOSPITAL   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

^d Parramatta Sexual Health Clinic   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE DERIVATIVE; CYTOKINE; DIPALMITOYLGLYCERYLCYSTEINE; GAMMA INTERFERON; GLYCOPROTEIN D; HLA DQ ANTIGEN; HLA DR ANTIGEN; TOLL LIKE RECEPTOR 2; UNCLASSIFIED DRUG; VIRUS ANTIGEN;

ARTICLE; CD4+ T LYMPHOCYTE; CELL CONTACT; CONTROLLED STUDY; DENDRITIC CELL; HERPES SIMPLEX; HERPES SIMPLEX VIRUS; HERPES SIMPLEX VIRUS 1; HERPES SIMPLEX VIRUS 2; HUMAN; HUMAN CELL; HUMAN TISSUE; LYMPHOCYTE ACTIVATION; NATURAL KILLER CELL; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; SKIN INFILTRATE; UPREGULATION;

ANTIGEN PRESENTATION; ANTIGENS, VIRAL; CD4-POSITIVE T-LYMPHOCYTES; CELL COMMUNICATION; CELLS, CULTURED; COCULTURE TECHNIQUES; DERMIS; FEMALE; HERPES GENITALIS; HERPES SIMPLEX VIRUS VACCINES; HERPESVIRUS 1, HUMAN; HERPESVIRUS 2, HUMAN; HLA-DQ ANTIGENS; HLA-DR ANTIGENS; HUMANS; IMMUNITY, INNATE; INTERFERON-GAMMA; KILLER CELLS, NATURAL; LIPOPEPTIDES; LYMPHOCYTE ACTIVATION; MALE; TOLL-LIKE RECEPTOR 2; UP-REGULATION; VIRAL ENVELOPE PROTEINS;

EID: 84860330860     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1103450     Document Type: Article

References (80)

1. Cunningham, A. L., R. R. Turner, A. C. Miller, M. F. Para, and T. C. Merigan. 1985. Evolution of recurrent herpes simplex lesions. An immunohistologic study. J. Clin. Invest. 75: 226-233. (Pubitemid 15171242)
2. Koelle, D. M., C. M. Posavad, G. R. Barnum, M. L. Johnson, J. M. Frank, and L. Corey. 1998. Clearance of HSV-2 from recurrent genital lesions correlates with infiltration of HSV-specific cytotoxic T lymphocytes. J. Clin. Invest. 101: 1500-1508. (Pubitemid 28166848)
3. Schiffer, J. T., L. Abu-Raddad, K. E. Mark, J. Zhu, S. Selke, D. M. Koelle, A. Wald, and L. Corey. 2010. Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes. Proc. Natl. Acad. Sci. USA 107: 18973-18978.
4. Mikloska, Z., and A. L. Cunningham. 1998. Herpes simplex virus type 1 glycoproteins gB, gC and gD are major targets for CD4 T-lymphocyte cytotoxicity in HLA-DR expressing human epidermal keratinocytes. J. Gen. Virol. 79: 353-361. (Pubitemid 28048440)
5. Mikloska, Z., and A. L. Cunningham. 2001. Alpha and gamma interferons inhibit herpes simplex virus type 1 infection and spread in epidermal cells after axonal transmission. J. Virol. 75: 11821-11826. (Pubitemid 33063273)
6. Mikloska, Z., M. Rückholdt, I. Ghadiminejad, H. Dunckley, M. Denis, and A. L. Cunningham. 2000. Monophosphoryl lipid A and QS21 increase CD8 T lymphocyte cytotoxicity to herpes simplex virus-2 infected cell proteins 4 and 27 through IFN-gamma and IL-12 production. J. Immunol. 164: 5167-5176. (Pubitemid 30305192)
7. Wakim, L. M., J. Waithman, N. van Rooijen, W. R. Heath, and F. R. Carbone. 2008. Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science 319: 198-202.
8. Zhu, J., F. Hladik, A. Woodward, A. Klock, T. Peng, C. Johnston, M. Remington, A. Magaret, D. M. Koelle, A. Wald, and L. Corey. 2009. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat. Med. 15: 886-892.
9. Stingl, G., K. Tamaki, and S. I. Katz. 1980. Origin and function of epidermal Langerhans cells. Immunol. Rev. 53: 149-174. (Pubitemid 11119137)
10. Sprecher, E., and Y. Becker. 1992. Detection of IL-1 beta, TNF-alpha, and IL-6 gene transcription by the polymerase chain reaction in keratinocytes, Langerhans cells and peritoneal exudate cells during infection with herpes simplex virus-1. Arch. Virol. 126: 253-269.
11. Allan, R. S., C. M. Smith, G. T. Belz, A. L. van Lint, L. M. Wakim, W. R. Heath, and F. R. Carbone. 2003. Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells. Science 301: 1925-1928. (Pubitemid 37229056)
12. Zhao, X., E. Deak, K. Soderberg, M. Linehan, D. Spezzano, J. Zhu, D. M. Knipe, and A. Iwasaki. 2003. Vaginal submucosal dendritic cells, but not Langerhans cells, induce protective Th1 responses to herpes simplex virus-2. J. Exp. Med. 197: 153-162. (Pubitemid 36152310)
13. Puttur, F. K., M. A. Fernandez, R. White, B. Roediger, A. L. Cunningham, W. Weninger, and C. A. Jones. 2010. Herpes simplex virus infects skin gamma delta T cells before Langerhans cells and impedes migration of infected Langerhans cells by inducing apoptosis and blocking E-cadherin downregulation. J. Immunol. 185: 477-487.
14. Bosnjak, L., M. Miranda-Saksena, D. M. Koelle, R. A. Boadle, C. A. Jones, and A. L. Cunningham. 2005. Herpes simplex virus infection of human dendritic cells induces apoptosis and allows cross-presentation via uninfected dendritic cells. J. Immunol. 174: 2220-2227. (Pubitemid 40223968)
15. Bukowski, J. F., and R. M. Welsh. 1986. The role of natural killer cells and interferon in resistance to acute infection of mice with herpes simplex virus type 1. J. Immunol. 136: 3481-3485. (Pubitemid 16113944)
16. Cheng, H., T. M. Tumpey, H. F. Staats, N. van Rooijen, J. E. Oakes, and R. N. Lausch. 2000. Role of macrophages in restricting herpes simplex virus type 1 growth after ocular infection. Invest. Ophthalmol. Vis. Sci. 41: 1402-1409. (Pubitemid 30261863)
17. Donaghy, H., L. Bosnjak, A. N. Harman, V. Marsden, S.K. Tyring, T.C. Meng, and A. L. Cunningham. 2009. Role for plasmacytoid dendritic cells in the immune control of recurrent human herpes simplex virus infection. J. Virol. 83: 1952-1961.
18. Sato, A., M. M. Linehan, and A. Iwasaki. 2006. Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells. Proc. Natl. Acad. Sci. USA 103: 17343-17348. (Pubitemid 44788971)
19. Lund, J., A. Sato, S. Akira, R. Medzhitov, and A. Iwasaki. 2003. Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J. Exp. Med. 198: 513-520. (Pubitemid 36976063)
20. Siegal, F. P., N. Kadowaki, M. Shodell, P. A. Fitzgerald-Bocarsly, K. Shah, S. Ho, S. Antonenko, and Y. J. Liu. 1999. The nature of the principal type 1 interferon-producing cells in human blood. Science 284: 1835-1837.
21. 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. (Pubitemid 38581474)
22. Moretta, L., G. Ferlazzo, C. Bottino, M. Vitale, D. Pende, M. C. Mingari, and A. Moretta. 2006. Effector and regulatory events during natural killer-dendritic cell interactions. Immunol. Rev. 214: 219-228. (Pubitemid 44707913)
23. Kadowaki, N., S. Antonenko, J. Y. Lau, and Y. J. Liu. 2000. Natural interferon alpha/beta-producing cells link innate and adaptive immunity. J. Exp. Med. 192: 219-226.
24. Kawamura, K., N. Kadowaki, T. Kitawaki, and T. Uchiyama. 2006. Virusstimulated plasmacytoid dendritic cells induce CD4+ cytotoxic regulatory T cells. Blood 107: 1031-1038. (Pubitemid 43156302)
25. Strowig, T., F. Brilot, and C. Münz. 2008. Noncytotoxic functions of NK cells: direct pathogen restriction and assistance to adaptive immunity. J. Immunol. 180: 7785-7791.
26. Moretta, A. 2005. The dialogue between human natural killer cells and dendritic cells. Curr. Opin. Immunol. 17: 306-311. (Pubitemid 40692667)
27. Ferlazzo, G., M. Pack, D. Thomas, C. Paludan, D. Schmid, T. Strowig, G. Bougras, W. A. Muller, L. Moretta, and C. Münz. 2004. Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc. Natl. Acad. Sci. USA 101: 16606-16611. (Pubitemid 39557760)
28. Hanna, J., T. Gonen-Gross, J. Fitchett, T. Rowe, M. Daniels, T. I. Arnon, R. Gazit, A. Joseph, K. W. Schjetne, A. Steinle, et al. 2004. Novel APC-like properties of human NK cells directly regulate T cell activation. J. Clin. Invest. 114: 1612-1623. (Pubitemid 40385552)
29. Hanna, J., and O. Mandelboim. 2007. When killers become helpers. Trends Immunol. 28: 201-206. (Pubitemid 46654871)
30. Adam, C., S. King, T. Allgeier, H. Braumüller, C. Lüking, J. Mysliwietz, A. Kriegeskorte, D. H. Busch, M. Röcken, and R. Mocikat. 2005. DC-NK cell cross talk as a novel CD4+ T-cell-independent pathway for antitumor CTL induction. Blood 106: 338-344. (Pubitemid 40967210)
31. Hart, O. M., V. Athie-Morales, G. M. O'Connor, and C. M. Gardiner. 2005. TLR7/8-mediated activation of human NK cells results in accessory cell-dependent IFN-gamma production. J. Immunol. 175: 1636-1642. (Pubitemid 41023066)
32. Andrews, D. M., C. E. Andoniou, A. A. Scalzo, S. L. van Dommelen, M. E. Wallace, M. J. Smyth, and M. A. Degli-Esposti. 2005. Cross-talk between dendritic cells and natural killer cells in viral infection. Mol. Immunol. 42: 547-555. (Pubitemid 39655967)
33. Megjugorac, N. J., H. A. Young, S. B. Amrute, S. L. Olshalsky, and P. Fitzgerald-Bocarsly. 2004. Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells. J. Leukoc. Biol. 75: 504-514. (Pubitemid 38316382)
34. Flacher, V., M. Bouschbacher, E. Verronèse, C. Massacrier, V. Sisirak, O. Berthier-Vergnes, B. de Saint-Vis, C. Caux, C. Dezutter-Dambuyant, S. Lebecque, and J. Valladeau. 2006. Human Langerhans cells express a specific TLR profile and differentially respond to viruses and Gram-positive bacteria. J. Immunol. 177: 7959-7967. (Pubitemid 44846312)
35. Hornung, V., S. Rothenfusser, S. Britsch, A. Krug, B. Jahrsdörfer, T. Giese, S. Endres, and G. Hartmann. 2002. 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: 4531-4537. (Pubitemid 34441357)
36. Morandi, B., G. Bougras, W. A. Muller, G. Ferlazzo, and C. Münz. 2006. NK cells of human secondary lymphoid tissues enhance T cell polarization via IFN-gamma secretion. Eur. J. Immunol. 36: 2394-2400. (Pubitemid 44420596)
37. Sørensen, L. N., L. S. Reinert, L. Malmgaard, C. Bartholdy, A. R. Thomsen, and S. R. Paludan. 2008. TLR2 and TLR9 synergistically control herpes simplex virus infection in the brain. J. Immunol. 181: 8604-8612.
38. Reske, A., G. Pollara, C. Krummenacher, D. R. Katz, and B. M. Chain. 2008. Glycoprotein-dependent and TLR2-independent innate immune recognition of herpes simplex virus-1 by dendritic cells. J. Immunol. 180: 7525-7536.
39. Stanberry, L. R., S. L. Spruance, A. L. Cunningham, D. I. Bernstein, A. Mindel, S. Sacks, S. Tyring, F. Y. Aoki, M. Slaoui, M. Denis, et al; GlaxoSmithKline Herpes Vaccine Efficacy Study Group. 2002. Glycoprotein-D- adjuvant vaccine to prevent genital herpes. N. Engl. J. Med. 347: 1652-1661. (Pubitemid 35340783)
40. Cohen, J. 2010. Immunology. Painful failure of promising genital herpes vaccine. Science 330: 304.
41. Kim, M., J. Taylor, J. Sidney, Z. Mikloska, N. Bodsworth, K. Lagios, H. Dunckley, K. Byth-Wilson, M. Denis, R. Finlayson, et al. 2008. Immunodominant epitopes in herpes simplex virus type 2 glycoprotein D are recognized by CD4 lymphocytes from both HSV-1 and HSV-2 seropositive subjects. J. Immunol. 181: 6604-6615.
42. Zeng, W., S. Ghosh, Y. F. Lau, L. E. Brown, and D. C. Jackson. 2002. Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immuno-contraceptive vaccines. J. Immunol. 169: 4905-4912. (Pubitemid 35217155)
43. Akira, S., S. Uematsu, and O. Takeuchi. 2006. Pathogen recognition and innate immunity. Cell 124: 783-801. (Pubitemid 43261452)
44. Kang, J. Y., X. Nan, M. S. Jin, S. J. Youn, Y. H. Ryu, S. Mah, S. H. Han, H. Lee, S. G. Paik, and J. O. Lee. 2009. Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity 31: 873-884.
45. Jin, M. S., S. E. Kim, J. Y. Heo, M. E. Lee, H. M. Kim, S. G. Paik, H. Lee, and J. O. Lee. 2007. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130: 1071-1082. (Pubitemid 47410281)
46. Schenk, M., J. T. Belisle, and R. L. Modlin. 2009. TLR2 looks at lipoproteins. Immunity 31: 847-849.
47. Bettahi, I., X. Zhang, R. E. Afifi, and L. BenMohamed. 2006. Protective immunity to genital herpes simplex virus type 1 and type 2 provided by self-adjuvanting lipopeptides that drive dendritic cell maturation and elicit a polarized Th1 immune response. Viral Immunol. 19: 220-236. (Pubitemid 44050321)
48. Mikloska, Z., L. Bosnjak, and A. L. Cunningham. 2001. Immature monocyte-derived dendritic cells are productively infected with herpes simplex virus type 1. J. Virol. 75: 5958-5964. (Pubitemid 32553126)
49. Zhu, J., D. M. Koelle, J. Cao, J. Vazquez, M. L. Huang, F. Hladik, A. Wald, and L. Corey. 2007. Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivation. J. Exp. Med. 204: 595-603. (Pubitemid 46457082)
50. Dalloul, A., E. Oksenhendler, O. Chosidow, P. Ribaud, G. Carcelain, S. Louvet, P. Massip, P. Lebon, and B. Autran. 2004. Severe herpes virus (HSV-2) infection in two patients with myelodysplasia and undetectable NK cells and plasmacytoid dendritic cells in the blood. J. Clin. Virol. 30: 329-336. (Pubitemid 38649102)
51. Nandakumar, S., S. N. Woolard, D. Yuan, B. T. Rouse, and U. Kumaraguru. 2008. Natural killer cells as novel helpers in anti-herpes simplex virus immune response. J. Virol. 82: 10820-10831. (Pubitemid 352691159)
52. Zauner, W., K. Lingnau, F. Mattner, A. von Gabain, and M. Buschle. 2001. Defined synthetic vaccines. Biol. Chem. 382: 581-595. (Pubitemid 32472170)
53. Warren, H. S., F. R. Vogel, and L. A. Chedid. 1986. Current status of immunological adjuvants. Annu. Rev. Immunol. 4: 369-388.
54. Ghielmetti, M., A. Reschner, M. Zwicker, and E. Padovan. 2005. Synthetic bacterial lipopeptide analogs: structural requirements for adjuvanticity. Immunobiology 210: 211-215. (Pubitemid 41025162)
55. Toth, I. 1994. A novel chemical approach to drug delivery: lipidic amino acid conjugates. J. Drug Target. 2: 217-239. (Pubitemid 24310625)
56. Koelle, D. M., H. Abbo, A. Peck, K. Ziegweid, and L. Corey. 1994. Direct recovery of herpes simplex virus (HSV)-specific T lymphocyte clones from recurrent genital HSV-2 lesions. J. Infect. Dis. 169: 956-961. (Pubitemid 24303211)
57. Cunningham, A. L., and T. C. Merigan. 1984. Leu-3+ T cells produce gamma-interferon in patients with recurrent herpes labialis. J. Immunol. 132: 197-202. (Pubitemid 14212130)
58. Brilot, F., T. Strowig, and C. Munz. 2008. NK cells interactions with dendritic cells shape innate and adaptive immunity. Front. Biosci. 13: 6443-6454.
59. Kassim, S. H., N. K. Rajasagi, B. W. Ritz, S. B. Pruett, E. M. Gardner, R. Chervenak, and S. R. Jennings. 2009. Dendritic cells are required for optimal activation of natural killer functions following primary infection with herpes simplex virus type 1. J. Virol. 83: 3175-3186.
60. Moretta, A., E. Marcenaro, S. Parolini, G. Ferlazzo, and L. Moretta. 2008. NK cells at the interface between innate and adaptive immunity. Cell Death Differ. 15: 226-233.
61. Andoniou, C. E., D. M. Andrews, and M. A. Degli-Esposti. 2006. Natural killer cells in viral infection: more than just killers. Immunol. Rev. 214: 239-250. (Pubitemid 44707915)
62. Zingoni, A., T. Sornasse, B. G. Cocks, Y. Tanaka, A. Santoni, and L. L. Lanier. 2004. Cross-talk between activated human NK cells and CD4+ T cells via OX40-OX40 ligand interactions. J. Immunol. 173: 3716-3724. (Pubitemid 39280732)
63. Assarsson, E., T. Kambayashi, J. D. Schatzle, S. O. Cramer, A. von Bonin, P. E. Jensen, H. G. Ljunggren, and B. J. Chambers. 2004. NK cells stimulate proliferation of T and NK cells through 2B4/CD48 interactions. J. Immunol. 173: 174-180. (Pubitemid 38797339)
64. Fehniger, T. A., M. A. Cooper, G. J. Nuovo, M. Cella, F. Facchetti, M. Colonna, and M. A. Caligiuri. 2003. CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood 101: 3052-3057. (Pubitemid 36857995)
65. Afkarian, M., J. R. Sedy, J. Yang, N. G. Jacobson, N. Cereb, S. Y. Yang, T. L. Murphy, and K. M. Murphy. 2002. T-bet is a STAT1-induced regulator of IL-12R expression in nïve CD4+ T cells. Nat. Immunol. 3: 549-557. (Pubitemid 34662307)
66. Lighvani, A. A., D. M. Frucht, D. Jankovic, H. Yamane, J. Aliberti, B. D. Hissong, B. V. Nguyen, M. Gadina, A. Sher, W. E. Paul, and J. J. O'Shea. 2001. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc. Natl. Acad. Sci. USA 98: 15137-15142. (Pubitemid 34013982)
67. bright NK cells. J. Leukoc. Biol. 80: 1529-1541. (Pubitemid 44904992)
68. Hanna, J., P. Bechtel, Y. Zhai, F. Youssef, K. McLachlan, and O. Mandelboim. 2004. Novel insights on human NK cells' immunological modalities revealed by gene expression profiling. J. Immunol. 173: 6547-6563. (Pubitemid 39541038)
69. Lauzon, N. M., F. Mian, R. MacKenzie, and A. A. Ashkar. 2006. The direct effects of Toll-like receptor ligands on human NK cell cytokine production and cytotoxicity. Cell. Immunol. 241: 102-112. (Pubitemid 44648026)
70. Martinez, J., X. Huang, and Y. Yang. 2010. Direct TLR2 signaling is critical for NK cell activation and function in response to vaccinia viral infection. PLoS Pathog. 6: e1000811.
71. Nesburn, A. B., I. Bettahi, X. Zhang, X. Zhu, W. Chamberlain, R. E. Afifi, S. L. Wechsler, and L. BenMohamed. 2006. Topical/mucosal delivery of sub-unit vaccines that stimulate the ocular mucosal immune system. Ocul. Surf. 4: 178-187. (Pubitemid 351907722)
72. Vyas, Y. M., H. Maniar, and B. Dupont. 2002. Visualization of signaling pathways and cortical cytoskeleton in cytolytic and noncytolytic natural killer cell immune synapses. Immunol. Rev. 189: 161-178. (Pubitemid 35448951)
73. Abraham, C., J. Griffith, and J. Miller. 1999. The dependence for leukocyte function-associated antigen-1/ICAM-1 interactions in T cell activation cannot be overcome by expression of high density TCR ligand. J. Immunol. 162: 4399-4405. (Pubitemid 29314835)
74. Barreira da Silva, R., C. Graf, and C. Münz. 2011. Cytoskeletal stabilization of inhibitory interactions in immunologic synapses of mature human dendritic cells with natural killer cells. Blood 118: 6487-6498.
75. Vyas, Y. M., H. Maniar, and B. Dupont. 2002. Cutting edge: differential segregation of the SRC homology 2-containing protein tyrosine phosphatase-1 within the early NK cell immune synapse distinguishes noncytolytic from cytolytic interactions. J. Immunol. 168: 3150-3154. (Pubitemid 34250373)
76. Monks, C. R., B. A. Freiberg, H. Kupfer, N. Sciaky, and A. Kupfer. 1998. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395: 82-86. (Pubitemid 28420234)
77. Revy, P., M. Sospedra, B. Barbour, and A. Trautmann. 2001. Functional antigen-independent synapses formed between T cells and dendritic cells. Nat. Immunol. 2: 925-931. (Pubitemid 32976164)
78. Asanuma, H., M. Sharp, H. T. Maecker, V. C. Maino, and A. M. Arvin. 2000. Frequencies of memory T cells specific for varicella-zoster virus, herpes simplex virus, and cytomegalovirus by intracellular detection of cytokine expression. J. Infect. Dis. 181: 859-866. (Pubitemid 30194466)
79. Watts, C. 2004. The exogenous pathway for antigen presentation on major histocompatibility complex class II and CD1 molecules. Nat. Immunol. 5: 685-692. (Pubitemid 39023297)
80. Bajénoff, M., B. Breart, A. Y. Huang, H. Qi, J. Cazareth, V. M. Braud, R. N. Germain, and N. Glaichenhaus. 2006. Natural killer cell behavior in lymph nodes revealed by static and real-time imaging. J. Exp. Med. 203: 619-631.