Cited by 346Pneumonia and Respiratory InfectionsT-cell and B-cell ImmunologyImmune responses and vaccinations

CD4 + T cells mediate antibody-independent acquired immunity to pneumococcal colonization

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Malley, Richard, Trzcinski, Krzysztof, Srivastava, Amit, Thompson, Claudette M., Anderson, Porter W., Lipsitch, Marc·2005·Proceedings of the National Academy of Sciences

Abstract

Acquired immunity to Streptococcus pneumoniae (pneumococcus) has long been assumed to depend on the presence of anticapsular antibodies. We found, however, that colonization with live pneumococci of serotypes 6B, 7F, or 14 protected mice against recolonization by any of the serotypes and that protection from acquisition of a heterologous or homologous strain did not depend on anticapsular antibody. Further, intranasal immunization by live pneumococcal colonization or by a killed, nonencapsulated whole-cell vaccine protected antibody-deficient mice against colonization, suggesting independence of antibodies to any pneumococcal antigens. Protection by intranasal immunization with whole-cell vaccine was completely abrogated in T cell-deficient mice, and in mice that were congenitally deficient in CD4 + T cells or depleted of these cells at the time of challenge. In contrast, mice congenitally deficient in, or depleted of, CD8 + T cells were fully protected. Protection in this model was observed beyond 2 months after immunization, arguing against innate or nonspecific immune mechanisms. Thus, we find that immunity to pneumococcal colonization can be induced in the absence of antibody, independent of the capsular type, and this protection requires the presence of CD4 + T cells at the time of challenge.

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  • Studies show that sterilizing immunity against carriage of Streptococcus pneumoniae in mice can be achieved by the transfer of T cells from donor mice exposed to S. pneumoniae.

    “Studies show that sterilizing immunity against carriage of S. pneumoniae in mice can be achieved by the transfer of T cells from donor mice exposed to S. pneumoniae40”

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  1. [1]World Health Organization (1998) Weekly Epidemiol. Records 73, 187-188. [Google Scholar]
  2. [2]Black, S., Shinefield, H., Fireman, B., Lewis, E., Ray, P., Hansen, J. R., Elvin, L., Ensor, K. M., Hackell, J., Siber, G., et al. (2000) Pediatr. Infect. Dis. J. 19, 187-195. [DOI] [PubMed] [Google Scholar]
  3. [3]Eskola, J., Kilpi, T., Palmu, A., Jokinen, J., Haapakoski, J., Herva, E., Takala, A., Kayhty, H., Karma, P., Kohberger, R., et al. (2001) N. Engl. J. Med. 344, 403-409. [DOI] [PubMed] [Google Scholar]
  4. [4]Kaplan, S. L., Mason, E. O., Jr., Wald, E. R., Schutze, G. E., Bradley, J. S., Tan, T. Q., Hoffman, J. A., Givner, L. B., Yogev, R. & Barson, W. J. (2004) Pediatrics 113, 443-449. [DOI] [PubMed] [Google Scholar]
  5. [5]Malley, R., Stack, A. M., Ferretti, M. L., Thompson, C. M. & Saladino, R. A. (1998) J. Infect. Dis. 178, 878-882. [DOI] [PubMed] [Google Scholar]
  6. [6]Dagan, R., Melamed, R., Muallem, M., Piglansky, L., Greenberg, D., Abramson, O., Mendelman, P. M., Bohidar, N. & Yagupsky, P. (1996) J. Infect. Dis. 174, 1271-1278. [DOI] [PubMed] [Google Scholar]
  7. [7]Austrian, R. (1986) J. Antimicrob. Chemother. 18, Suppl. A, 35-45. [DOI] [PubMed] [Google Scholar]
  8. [9]Malley, R., Lipsitch, M., Stack, A., Saladino, R., Fleisher, G., Pelton, S., Thompson, C., Briles, D. E. & Anderson, P. (2001) Infect. Immun. 69, 4870-4873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. [10]Malley, R., Morse, S. C., Leite, L. C. C., Mattos Areas, A. P., Ho, P. L., Kubrusly, F. S., Almeida, I. C. & Anderson, P. (2004) Infect. Immun. 72, 4290-4292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. [11]McCool, T. L. & Weiser, J. N. (2004) Infect. Immun. 72, 5807-5813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. [12]Trzcinski, K., Thompson, C. M. & Lipsitch, M. (2003) Appl. Environ. Microbiol. 69, 7364-7370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. [13]Kitamura, D., Roes, J., Kuhn, R. & Rajewsky, K. (1991) Nature 350, 423-426. [DOI] [PubMed] [Google Scholar]
  13. [14]Zijlstra, M., Bix, M., Simister, N. E., Loring, J. M., Raulet, D. H. & Jaenisch, R. (1990) Nature 344, 742-746. [DOI] [PubMed] [Google Scholar]
  14. [15]Grusby, M. J., Auchincloss, H., Jr., Lee, R., Johnson, R. S., Spencer, J. P., Zijlstra, M., Jaenisch, R., Papaioannou, V. E. & Glimcher, L. H. (1993) Proc. Natl. Acad. Sci. USA 90, 3913-3917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. [16]Penttila, J. M., Anttila, M., Varkila, K., Puolakkainen, M., Sarvas, M., Makela, P. H. & Rautonen, N. (1999) Immunology 97, 490-496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. [17]Kadioglu, A., Coward, W., Colston, M. J., Hewitt, C. R. & Andrew, P. W. (2004) Infect. Immun. 72, 2689-2697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. [19]Anderson, P., Pichichero, M. E. & Insel, R. A. (1985) J. Pediatr. 107, 346-351. [DOI] [PubMed] [Google Scholar]
  18. [20]Ahman, H., Kayhty, H., Lehtonen, H., Leroy, O., Froeschle, J. & Eskola, J. (1998) Pediatr. Infect. Dis. J. 17, 211-216. [DOI] [PubMed] [Google Scholar]
  19. [21]Park, H. S., Costalonga, M., Reinhardt, R. L., Dombek, P. E., Jenkins, M. K. & Cleary, P. P. (2004) Eur. J. Immunol. 34, 2843-2853. [DOI] [PubMed] [Google Scholar]
  20. [22]Kadioglu, A., Gingles, N. A., Grattan, K., Kerr, A., Mitchell, T. J. & Andrew, P. W. (2000) Infect. Immun. 68, 492-501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. [23]Lederman, H. M. & Winkelstein, J. A. (1985) Medicine (Baltimore) 64, 145-156. [PubMed] [Google Scholar]
  22. [24]O'Brien, K. L. & Dagan, R. (2003) Vaccine 21, 1815-1825. [DOI] [PubMed] [Google Scholar]
  23. [25]Rapola, S., Jantti, V., Haikala, R., Syrjanen, R., Carlone, G. M., Sampson, J. S., Briles, D. E., Paton, J. C., Takala, A. K., Kilpi, T. M. & Kayhty, H. (2000) J. Infect. Dis. 182, 1146-1152. [DOI] [PubMed] [Google Scholar]
  24. [26]Skov Sorensen, U. B., Blom, J., Birch-Andersen, A. & Henrichsen, J. (1988) Infect. Immun. 56, 1890-1896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. [27]Kim, J. O. & Weiser, J. N. (1998) J. Infect. Dis. 177, 368-377. [DOI] [PubMed] [Google Scholar]
  26. [28]Cundell, D. R., Gerard, N. P., Gerard, C., Idanpaan-Heikkila, I. & Tuomanen, E. I. (1995) Nature 377, 435-438. [DOI] [PubMed] [Google Scholar]
  27. [29]Geginat, G., Lalic, M., Kretschmar, M., Goebel, W., Hof, H., Palm, D. & Bubert, A. (1998) J. Immunol. 160, 6046-6055. [PubMed] [Google Scholar]
  28. [30]de Jong, R., Altare, F., Haagen, I. A., Elferink, D. G., Boer, T., van Breda Vriesman, P. J., Kabel, P. J., Draaisma, J. M., van Dissel, J. T., Kroon, F. P., et al. (1998) Science 280, 1435-1438. [DOI] [PubMed] [Google Scholar]
  29. [31]Malley, R., Henneke, P., Morse, S. C., Cieslewicz, M. J., Lipsitch, M., Thompson, C. M., Kurt-Jones, E., Paton, J. C., Wessels, M. R. & Golenbock, D. T. (2003) Proc. Natl. Acad. Sci. USA 100, 1966-1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. [32]Agrawal, S., Agrawal, A., Doughty, B., Gerwitz, A., Blenis, J., Van Dyke, T. & Pulendran, B. (2003) J. Immunol. 171, 4984-4989. [DOI] [PubMed] [Google Scholar]
  31. [33]Kolls, J. K. & Linden, A. (2004) Immunity 21, 467-476. [DOI] [PubMed] [Google Scholar]
  32. [34]Happel, K. I., Zheng, M., Young, E., Quinton, L. J., Lockhart, E., Ramsay, A. J., Shellito, J. E., Schurr, J. R., Bagby, G. J., Nelson, S. & Kolls, J. K. (2003) J. Immunol. 170, 4432-4436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. [35]Whitney, C. G., Farley, M. M., Hadler, J., Harrison, L. H., Bennett, N. M., Lynfield, R., Reingold, A., Cieslak, P. R., Pilishvili, T., Jackson, D., et al. (2003) N. Engl. J. Med. 348, 1737-1746. [DOI] [PubMed] [Google Scholar]
  34. [36]Briles, D. E., Tart, R. C., Swiatlo, E., Dillard, J. P., Smith, P., Benton, K. A., Ralph, B. A., Brooks-Walter, A., Crain, M. J., Hollingshead, S. K. & McDaniel, L. S. (1998) Clin. Microbiol. Rev. 11, 645-657. [DOI] [PMC free article] [PubMed] [Google Scholar]

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Authors
Malley, R., Trzcinski, K., Srivastava, A., Thompson, C. M., Anderson, P. W., & Lipsitch, M.
Affiliations
  • Boston Children's Hospital (US)
  • Division of Infectious Diseases, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, MA 02115; Departments of Epidemiology and Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02215; and Department of Pediatrics, University of Rochester, Rochester, NY 14627
Venue
Proceedings of the National Academy of Sciences
Published
2005-03-21
Volume
102
Issue
13
Pages
4848-4853
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2138424202
Cited by
346
References
35
Citations by year
2026: 12 · 2025: 9 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 11 · 2018: 15 · 2017: 27 · 2016: 14 · 2015: 18 · 2014: 23 · 2013: 22 · 2012: 29
FWCI
14.57
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
National Institute of Allergy and Infectious Diseases (K08 AI51526-01, K08AI051526, AI07061-26, R01AI048935, T32AI007061)
Topics
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
Streptococcus pneumoniae, pneumococcal carriage, CD4+ T cells, antibody-independent immunity, adaptive immunity, CD8+ T cells, whole-cell vaccine, intranasal immunization, antibody deficiency, T cell-deficient mice, serotype 6B, serotype 7F, serotype 14, mucosal immunity
MeSH terms
Administration, Intranasal, Animals, Enzyme-Linked Immunosorbent Assay, Female, Immunity, Cellular, Mice, Inbred C57BL, Pneumococcal Infections, Species Specificity, Streptococcus pneumoniae, Time Factors, CD4-Positive T-Lymphocytes, Streptococcal Vaccines, Mice

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