What role does the route of immunization play in the generation of protective immunity against mucosal pathogens?

Journal of Immunology

Volumn 183, Issue 11, 2009, Pages 6883-6892

  Belyakov, Igor M ^a   Ahlers, Jeffrey D ^b  

^a MIDWEST RESEARCH INSTITUTE   (United States)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BCG VACCINE; CHOLERA VACCINE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G1; INACTIVATED VACCINE; INFLUENZA VACCINE; LIVE VACCINE; NEUTRALIZING ANTIBODY; POLIOMYELITIS VACCINE; TYPHOID VACCINE; VACCINE;

ADAPTIVE IMMUNITY; BACTERIAL INFECTION; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CHOLERA; CLINICAL TRIAL; DENDRITIC CELL; DRUG DOSE REGIMEN; DRUG EFFICACY; HUMAN; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOCOMPETENT CELL; IMMUNOGENICITY; INFLUENZA A (H1N1); INNATE IMMUNITY; INTESTINE EPITHELIUM; INTESTINE INFECTION; LUNG TUBERCULOSIS; MEMORY CELL; MYCOSIS; NONHUMAN; PARASITOSIS; POLIOMYELITIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; TH17 CELL; TYPHOID FEVER; UNSPECIFIED SIDE EFFECT; VACCINATION; VIRUS REPLICATION; VIRUS TRANSMISSION; ANIMAL; DRUG ADMINISTRATION ROUTE; IMMUNOLOGY; INFECTION; MUCOSAL IMMUNITY;

ANIMALS; DRUG ADMINISTRATION ROUTES; HUMANS; IMMUNITY, MUCOSAL; INFECTION; VACCINES;

EID: 73349104433     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0901466     Document Type: Review

References (93)

1. Swartz, T. A., M. S. Green, R. Handscher, D. Sofer, M. Cohen-Dar, T. Shohat, S. Habib, E. Barak, Z. Dror, E. Somekh, T. Peled-Leviathan, et al. 2008. Intestinal immunity following a combined enhanced inactivated polio vaccine/oral polio vaccine programme in Israel. Vaccine 26: 1083-1090.
2. John, T. J. 2001. Anomalous observations on IPV and OPV vaccination. Dev. Biol. (Basel) 105: 197-208.
3. Kaul, D., and P. L. Ogra. (1998) Mucosal responses to parenteral and mucosal vaccines. Dev. Biol. Stand. 95: 141-146.
4. Jang, M. H., M. N. Kweon, K. Iwatani, M. Yamamoto, K. Terahara, C. Sasakawa, T. Suzuki, T. Nochi, Y. Yokota, P. D. Rennert, et al. 2004. Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc. Natl. Acad. Sci. USA 101: 6110-6115.
5. + cells. Nat. Med. 8: 150-156.
6. Stahl-Hennig, C., R. M. Steinman, K. Tenner-Racz, M. Pope, N. Stolte, K. Mätz-Rensing, G. Grobschupff, B. Raschdorff, G. Hunsmann, and P. Racz. 1999. Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus. Science 285: 1261-1265. (Pubitemid 29398612)
7. Geijtenbeek, T. B., D. S. Kwon, R. Torensma, S. J. van Vliet, G. C. van Duijnhoven, J. Middel, I. L. Cornelissen, H. S. Nottet, V. N. KewalRamani, D. R. Littman, et al. 2000. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances transinfection of T cells. Cell 100: 587-597.
8. Abel, K., B. Pahar, K. K. Van Rompay, L. Fritts, C. Sin, K. Schmidt, R. Colón, M. McChesney, and M. L. Marthas. 2006. Rapid virus dissemination in infant macaques after oral simian immunodeficiency virus exposure in the presence of local innate immune responses. J. Virol. 80: 6357-6367. (Pubitemid 43927439)
9. Hladik, F., P. Sakchalathorn, L. Ballweber, G. Lentz, M. Fialkow, D. Eschenbach, and M. J. McElrath. 2007. Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 26: 257-270. (Pubitemid 46329434)
10. Belyakov, I. M., J. D. Ahlers, and J. A. Berzofsky. 2004 Mucosal AIDS vaccines: current status and future directions. Expert Rev. Vaccines 3(4 Suppl.): S65-S73. (Pubitemid 39120627)
11. Berzofsky, J. A., J. D. Ahlers, and I. M. Belyakov. 2001. Strategies for designing and optimizing new generation vaccines. Nat. Rev. Immunol. 1: 209-219. (Pubitemid 33741959)
12. Ichinohe, T., H. K. Lee, Y. Ogura, R. Flavell, and A. Iwasaki. 2009. Inflammasome recognition of influenza virus is essential for adaptive immune responses. J. Exp. Med. 206: 79-87.
13. Spira, A. I., P. A. Marx, B. K. Patterson, J. Mahoney, R. A. Koup, S. M. Wolinsky, and D. D. Ho. 1996. Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J. Exp. Med. 183: 215-225.
14. + CTLs in delay of AIDS-viral dissemination from mucosa. Blood 107: 3258-3264.
15. + T cell depletion and viral replication in SIV infection. Science 280: 427-431.
16. Ogra, P. L. 1984. Mucosal immune response to poliovirus vaccines in childhood. Rev. Infect. Dis. 6(Suppl. 2): S361-S368.
17. Onorato, I. M., J. F. Modlin, A. M. McBean, M. L. Thomas, G. A. Losonsky, and R. H. Bernier. 1991. Mucosal immunity induced by enhance-potency inactivated and oral polio vaccines. J. Infect. Dis. 163: 1-6.
18. Sundström, P., S. B. Lundin, L. A. Nilsson, and M. Quiding-Järbrink. 2008. Human IgA-secreting cells induced by intestinal, but not systemic, immunization respond to CCL25 (TECK) and CCL28 (MEC). Eur. J. Immunol. 38: 3327-3338.
19. Stephenson, I., M. C. Zambon, A. Rudin, A. Colegate, A. Podda, R. Bugarini, G. Del Giudice, A. Minutello, S. Bonnington, J. Holmgren, et al. 2006. Phase I evaluation of intranasal trivalent inactivated influenza vaccine with nontoxigenic Escherichia coli enterotoxin and novel biovector as mucosal adjuvants, using adult volunteers. J. Virol. 80: 4962-4970.
20. Viret, J. F., D. Favre, B. Wegmüller, C. Herzog, J. U. Que, S. J. Cryz, Jr., and A. B. Lang. 1999. Mucosal and systemic immune responses in humans after primary and booster immunizations with orally administered invasive and noninvasive live attenuated bacteria. Infect. Immun. 67: 3680-3685.
21. Belshe, R. B., P. M. Mendlelman, J. Treanor, J. King, W. C. Gruber, P. Piedra, D. I. Bernstein, F. G. Hayden, K. Kotloff, K. Zangwill, et al. 1998. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N. Engl. J. Med. 338: 1405-1412.
22. Nichol, K. L., P. M. Mendelman, K. P. Mallon, L. A. Jackson, G. J. Gorse, R. B. Belshe, W. P. Glezen, and J. Wittes. 1999. Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. J. Am. Med. Assoc. 282: 137-144.
23. Agnello, D., C. A. Hervé, A. Lavaux, M. Darniot, P. Guillon, A. Charpilienne, and P. Pothier. 2006. Intrarectal immunization with rotavirus 2/6 virus-like particles induces an antirotavirus immune response localized in the intestinal mucosa and protects against rotavirus infection in mice. J. Virol. 80: 3823-3832.
24. Perry, R. T., C. V. Plowe, B. Koumaré, F. Bougoudogo, K. L. Kotloff, G. A. Losonsky, S. S. Wasserman, and M. M. Levine. 1998. A single dose of live oral cholera vaccine CVD 103-HgR is safe and immunogenic in HIV-infected and HIV-noninfected adults in Mali. Bull. World Health Organ. 76: 63-71.
25. Andersen, C. S., J. Dietrich, E. M. Agger, N. Y. Lycke, K. Lövgren, and P. Andersen. 2007. The combined CTA1-DD/ISCOMs vector is an effective intranasal adjuvant for boosting prior Mycobacterium bovis BCG immunity to Mycobacterium tuberculosis. Infect. Immun. 75: 408-416.
26. McNeal, M. M., M. Basu, J. A. Bean, J. D. Clements, N. Y. Lycke, A. Ramne, B. Löwenadler, A. H. Choi, and R. L. Ward. 2007. Intrarectal immunization of mice with VP6 and either LT(R192G) or CTA1-DD as adjuvant protects against fecal rotavirus shedding after EDIM challenge. Vaccine 25: 6224-6231.
27. Goonetilleke, N. P., H. McShane, C. M. Hannan, R. J. Anderson, R. H. Brookes, and A. V. S. Hill. 2003. Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guerin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J. Immunol. 171: 1602-1609.
28. Jeyanathan, M., J. Mu, K. Kugathasan, X. Zhang, D. Damjanovic, C. Small, M. Divangahi, B. J. Petrof, C. Hogaboam, and Z. Xing. 2008. Airway delivery of soluble mycobacterial antigens restores protective mucosal immunity by single intramuscular plasmid DNA tuberculosis vaccination: role of proinflammatory signals in the lung. J. Immunol. 181: 5618-5626.
29. Wang, J., L. Thorson, R. W. Stokes, M. Santosuosso, K. Huygen, A. Zganiacz, M. Hitt, and Z. Xing. 2004. Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis. J. Immunol. 173: 6357-6365. (Pubitemid 39487795)
30. Neutra, M. R., and P. A. Kozlowski. 2006 Mucosal vaccines: the promise and the challenge. Nat. Rev. Immunol. 6: 148-158.
31. + CTLs in mucosal sites and HIV infection: moving forward toward a mucosal AIDS vaccine. Trends Immunol. 29: 574-585.
32. Ahlers, J. D., and I. M. Belyakov. 2009. Strategies for optimizing targeting and delivery of mucosal HIV vaccines. Eur. J. Immunol. 39: 2657-2669.
33. Suzich, J. A., S. J. Ghim, F. J. Palmer-Hill, W. I. White, J. K. Tamura, J. A. Bell, J. A. Newsome, A. B. Jenson, and R. Schlegel. 1995. Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas. Proc. Nat. Acad. Sci. USA 92: 11553-11557.
34. Haan, L., W. R. Verweij, M. Holtrop, R. Brands, G. J. van Scharrenburg, A. M. Palache, E. Agsteribbe, and J. Wilschut. 2001. Nasal or intramuscular immunization of mice with influenza subunit antigen and the B subunit of Escherichia coli heat-labile toxin induces IgA- or IgG-mediated protective mucosal immunity. Vaccine 19: 2898-2907. (Pubitemid 32244283)
35. Morello, C. S., M. Ye, S. Hung, L. A. Kelley, and D. H. Spector. 2005. Systemic priming-boosting immunization with a trivalent plasmid DNA and inactivated murine cytomegalovirus (MCMV) vaccine provides long-term protection against viral replication following systemic or mucosal MCMV challenge. J. Virol. 79: 159-175.
36. + T-cell loss and reduces both systemic and mucosal SHIVKU2 RNA levels. J. Virol. 80: 3732-3742.
37. + T cell functionality and mucosal homing. Virology 367: 156-167.
38. + T cell responses in the gut. Vaccine 25: 2187-2193.
39. + T lymphocytes to mucosal surfaces following intramuscular vaccination. J. Immunol. 181: 4188-4198.
40. Hansen, S. G., C. Vieville, N. Whizin, L. Coyne-Johnson, D. C. Siess, D. D. Drummond, A. W. Legasse, M. K. Axthelm, K. Oswald, C. M. Trubey, et al. 2009. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat. Med. 15: 293-299.
41. Tineke, M., P. T. Herremans, J. H. J. Reimerink, A. M. Buisman, T. G. Kimman, and M. P. G. Koopmans. 1999. Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on previous mucosal contact with live virus. J. Immunol. 162: 5011-5018.
42. Belyakov, I. M., Z. Hel, B. Kelsall, V. A. Kuznetsov, J. D. Ahlers, J. Nacsa, D. I. Watkins, T. M. Allen, A. Sette, J. Altman, et al. 2001. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nat. Med. 7: 1320-1326.
43. Gallichan, W. S., and K. L. Rosenthal. 1996. Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization. J. Exp. Med. 184: 1879-1890.
44. Revaz, V., J. Benyacoub, W. M. Kast, J. T. Schiller, P. De Grandi, and D. Nardelli-Haefliger. 2001. Mucosal vaccination with a recombinant Salmonella typhimurium expressing human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) or HPV16 VLPs purified from insect cells inhibits the growth of HPV16-expressing tumor cells in mice. Virology 279: 354-360.
45. Kozlowski, P. A., S. Cu-Uvin, M. R. Neutra, and T. P. Flanigan. 1997. Comparison of the oral, rectal, and vaginal immunization routes for induction of antibodies in rectal and genital tract secretions of women. Infect. Immun. 65: 1387-1394.
46. + T cells. J. Immunol. 178: 7211-7221.
47. Li, Z., M. Zhang, C. Zhou, X. Zhao, N. Iijima, and F. R. Frankel. 2008. Novel vaccination protocol with two live mucosal vectors elicits strong cell-mediated immunity in the vagina and protects against vaginal virus challenge. J. Immunol. 180: 2504-2513.
48. + T cells with regime-dependent cytokine/ granzyme B profiles. J. Immunol. 178: 2370-2379.
49. Amorij, J. P., V. Saluja, A. H. Petersen, W. L. Hinrichs, A. Huckriede, and H. W. Frijlink. 2007. Pulmonary delivery of an inulin-stabilized influenza subunit vaccine prepared by spray-freeze drying induces systemic, mucosal humoral as well as cell-mediated immune responses in BALB/c mice. Vaccine 25: 8707-8717.
50. + T cell responses. J. Immunol. 166: 1106-1113.
51. Belyakov, I. M., M. A. Derby, J. D. Ahlers, B. L. Kelsall, P. Earl, B. Moss, W. Strober, and J. F. Berzofsky. 1998. Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge. Proc. Natl. Acad. Sci. USA 95: 1709-1714.
52. + cytotoxic T lymphocytes for resistance to mucosal-viral transmission in mice and enhancement of resistance by local administration of IL-12. J. Clin. Invest. 102: 2072-2081.
53. Kantele, A., M. Häkkinen, Z. Moldoveanu, A. Lu, E. Savilahti, R. D. Alvarez, S. Michalek, and J. Mestecky. 1998. Differences in immune responses induced by oral and rectal immunizations with Salmonella typhi Ty21a: evidence for compartmentalization within the common mucosal immune system in humans. Infect. Immun. 66: 5630-5635.
54. Bienenstock, J., A. D. Befus, M. McDermott, S. Mirski, K. Rosenthal, and A. Tagliabue. 1983. The mucosal immunological network: compartmentalization of lymphocytes, natural killer cells, and mast cells. Ann. NY Acad. Sci. 409: 164-170.
55. Koprowski, H. 2006. First decade (1950 -1960) of studies and trials with the polio vaccine. Biologicals 34: 81-86.
56. World health organization collaborative study group on oral and inactivated poliovirus vaccines. 1996. Combined immunization of infants with oral and inactivated poliovirus vaccines: results of a randomized trial in The Gambia, Oman, and Thailand. Bull. World Health Organ. 74: 253-268.
57. Faden, H. 1993. Poliovirus vaccination: a trilogy. J. Infect. Dis. 168: 25-28.
58. Knolle, H. T., A. Egli, and U. Candrian. 2004. [The perspective of global eradication of poliomyelitis]. Gesundheitswesen 66: 1-6.
59. Ichinohe, A. Iwasaki, and H. Hasegawa. 2008. Innate sensors of influenza virus: clues to developing better intranasal vaccines. Expert Rev. Vaccines. 7: 1435-1445.
60. Perrone, L. A., A. Ahmad, A. Vequilla, X. Lu, G. Smith, J. M. Katz, P. Pushko, and T. M. Tumpey. 2009. Intranasal vaccination with 1918 influenza virus-like particles protects mice and ferrets from lethal 1918 and H5N1 influenza virus challenge. J. Virol. 83: 5726-5734.
61. Wee, J. L., J. P. Scheerlinck, K. J. Snibson, S. Edwards, M. Pearse, C. Quinn, and P. Sutton. 2008. Pulmonary delivery of ISCOMATRIX influenza vaccine induces both systemic and mucosal immunity with antigen dose sparing. Mucosal Immunol. 1: 489-496.
62. Straight, T. M., M. G. Ottolini, G. A. Prince, and M. C. Eichelberger. 2008. Antibody contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats. Virol. J. 5: 44.
63. Guthrie, T., C. G. Hobbs, V. Davenport, R. E. Horton, R. S. Heyderman, and N. A. Williams. 2004. Parenteral influenza vaccination influences mucosal and systemic T cell-mediated immunity in healthy adults. J. Infect. Dis. 190: 1927-1935.
64. Ambrose, C. S., C. Luke, and K. Coelingh. 2008. Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza. Influenza Other Respi. Viruses 2: 193-202.
65. Kantele, A., J. M. Kantele, E. Savilahti, M. Westerholm, H. Arvilommi, A. Lazarovits, E. C. Butcher, and P. H. Makela. 1997. Homing potentials of circulating lymphocytes in humans depend on the site of activation: oral, but not parenteral, typhoid vaccination induces circulating antibody-secreting cells that all bear homing receptors directing them to the gut. J. Immunol. 158: 574-579.
66. Chabot, S. M., M. Shawi, T. Eaves-Pyles, and M. R. Neutra. 2008. Effects of flagellin on the functions of follicle-associated epithelium. J. Infect. Dis. 198: 907-910.
67. Engels, E. A., and J. Lau. 2000. Vaccines for preventing typhoid fever. Cochrane Database Syst Rev. CD001261.
68. Losonsky, G. A., C. O. Tacket, S. S. Wasserman, J. B. Kaper, and M. M. Levine. 1993. Secondary Vibrio cholerae-specific cellular antibody responses following wild-type homologous challenge in people vaccinated with CVD 103-HgR live oral cholera vaccine: changes with time and lack of correlation with protection. Infect. Immun. 61: 729-733.
69. Santosuosso, M., X. Zhang, S. McCormick, J. Wang, M. Hitt, and Z. Xing. 2005. Mechanisms of mucosal and parenteral tuberculosis vaccinations: adenoviral-based mucosal immunization preferentially elicits sustained accumulation of immune protective CD4 and CD8 T cells within the airway lumen. J. Immunol. 174: 7986-7994. (Pubitemid 40806309)
70. Roediger, E. K., K. Kugathasan, X. Zhang, B. D. Lichty, and Z. Xing. 2008. Heterologous boosting of recombinant adenoviral prime immunization with a novel vesicular stomatitis virus-vectored tuberculosis vaccine. Mol. Ther. 16: 1161-1169.
71. Kaul, R., F. Plummer, M. Clerici, M. Bomsel, L. Lopalco, and K. Broliden. 2001. Mucosal IgA in exposed, uninfected subjects: evidence for a role in protection against HIV infection. AIDS 15: 431-432. (Pubitemid 32163839)
72. Hessell, A. J., P. Poignard, M. Hunter, L. Hangartner, D. M. Tehrani, W. K. Bleeker, P. W. Parren, P. A. Marx, and D. R. Burton. 2009. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat. Med. 15: 951-954.
73. + CTL in intestinal mucosa following mucosal, systemic or mixed prime-boost immunization. Virology 381: 106-115.
74. Masopust, D., S.-J. Ha, V. Vezys, and R. Ahmed. 2006. Stimulation history dictates memory CD8 T cell phenotype: implications for prime-boost vaccination. J. Immunol. 177: 831-839.
75. Li, Q., P. J. Skinner, S. J. Ha, L. Duan, T. L. Mattila, A. Hage, C. White, D. L. Barber, L. O'Mara, P. J. Southern, et al. 2009. Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection. Science 323: 1726-1729.
76. Coombes, J. L., and F. Powrie. 2008. Dendritic cells in intestinal immune regulation. Nat. Rev. Immunol. 8: 435-446. (Pubitemid 351733420)
77. + dendritic cells in the regulation of tissue-selective T cell homing. J. Exp. Med. 202: 1063-1073.
78. Lee, H. K., M. Zamora, M. M. Linehan, N. Iijima, D. Gonzalez, A. Haberman, and A. Iwasaki. 2009. Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection. J. Exp. Med. 206: 359-370.
79. Kelsall, B. 2008. Recent progress in understanding the phenotype and function of intestinal dendritic cells and macrophages. Mucosal Immunol. 1: 460-469.
80. Belyakov, I. M., S. A. Hammond, J. D. Ahlers, G. M. Glenn, and J. A. Berzofsky. 2004. Transcutaneous immunization induces mucosal CTL and protective immunity by migration of primed skin dendritic cells. J. Clin. Invest. 113: 998-1007.
81. Ahlers, J. D., and I. M. Belyakov. 2009 Strategies for recruiting and targeting dendritic cells for optimizing HIV vaccines. Trends Mol. Med. 15: 263-274.
82. Rimoldi, M., M. Chieppa, P. Larghi, M. Vulcano, P. Allavena, and P. Rescigno. 2005. Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different. Blood 106: 2818-2826. (Pubitemid 41510759)
83. Salazar-Gonzalez, R. M., J. H. Niess, D. J. Zammit, R. Ravindran, A. Srinivasan, J. R. Maxwell, T. Stoklasek, R. Yadav, I. R. Williams, X. Gu, et al. 2006. CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. Immunity. 24: 623-632.
84. Urry, Z., E. Xystrakis, D. F. Richards, J. McDonald, Z. Sattar, D. J. Cousins, C. J. Corrigan, E. Hickman, Z. Brown, and C. M. Hawrylowicz. 2009. Ligation of TLR9 induced on human IL-10-secreting Tregs by 1α,25- dihydroxyvitamin D3 abrogates regulatory function. J. Clin. Invest. 119: 387-398.
85. Sutmuller, R. P., M. H. den Brok, M. Kramer, E. J. Bennink, L. W. Toonen, B. J. Kullberg, L. A. Joosten, S. Akira, M. G. Netea, and G. J. Adema. 2006. Toll-like receptor 2 controls expansion and function of regulatory T cells. J. Clin. Invest. 116: 485-494. (Pubitemid 43228366)
86. + regulatory T cell function. Science 309: 1380-1384.
87. Liu, G., S. Burns, G. Huang, K. Boyd, R. L. Proia, R. A. Flavell, and H. Chi. 2009. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat. Immunol. 10: 769-777.
88. + T cell responses. PLoS One 4: e4204.
89. + dendritic cells. Nat. Immunol. 10: 488-495.
90. Uematsu, S., J. Fujimoto, M. H. Jang, B. G. Yang, Y. J. Jung, M. Nishiyama, S. Sato, T. Tsujimura, M. Yamamoto, Y. Yokota, et al. 2008. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat. Immunol. 9: 769-776. (Pubitemid 351859160)
91. McKinstry, K. K., et al. 2009. IL-10 deficiency unleashes an influenza-specific Th17 response and enhances survival against high-dose challenge. J. Immunol. 182: 7353-7363.
92. + memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection. Mucosal Immunol. 2: 439-449.
93. Snyder, J. T., M. A. Alexander-Miller, J. A. Berzofsky, and I. M. Belyakov. 2003. Molecular mechanisms and biological significance of CTL avidity. Current HIV Res. 1: 287-294.