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

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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

DOI 10.1073/pnas.0501254102PMC PMC555733

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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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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
ORCID: Malley, Richard
Srivastava, Amit
Lipsitch, Marc
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2005-03-21
Volume: 102
Issue: 13
Pages: 4848-4853
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0501254102
PMC: PMC555733
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: green
www.ncbi.nlm.nih.gov
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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CD4 + T cells mediate antibody-independent acquired immunity to pneumococcal colonization

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