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A Suction Blister Protocol to Study Human T-cell Recall Responses In Vivo
Published on: August 11, 2018
CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization
Richard Malley1, Krzysztof Trzcinski, Amit Srivastava
1Division of Infectious Diseases, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. richard.malley@childrens.harvard.edu
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.
Insights
Acquired immunity to Streptococcus pneumoniae (pneumococcus) does not require anticapsular antibodies. Instead, CD4(+) T cells are crucial for protection against pneumococcal colonization, independent of antibody presence.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Acquired immunity to Streptococcus pneumoniae (pneumococcus) was traditionally attributed to anticapsular antibodies.
- The role of non-antibody-mediated immunity in pneumococcal colonization resistance was not well understood.
Purpose of the Study:
- To investigate the role of antibodies and T cells in acquired immunity to pneumococcal colonization.
- To determine if protection against pneumococcus colonization is antibody-dependent.
Main Methods:
- Mice were colonized with live pneumococci or immunized with whole-cell vaccines.
- Immunity was assessed in antibody-deficient, T cell-deficient (CD4+ and CD8+), and wild-type mice.
- Protection against homologous and heterologous strains was evaluated.
Main Results:
- Colonization with live pneumococci conferred protection independent of anticapsular antibodies.
- Intranasal immunization with whole-cell vaccine protected antibody-deficient mice.
- Protection was abrogated in CD4(+) T cell-deficient mice but not in CD8(+) T cell-deficient mice.
- Immunity persisted for over 2 months, suggesting specific adaptive immune mechanisms.
Conclusions:
- Immunity to pneumococcal colonization can be induced without anticapsular antibodies.
- CD4(+) T cells are essential for protective immunity against pneumococcal colonization.
- This T cell-dependent immunity is independent of pneumococcal serotype.
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