Antigen-Specific IFN-γ/IL-17-Co-Producing CD4+ T-Cells are the Determinants for Protective Efficacy of Tuberculosis Subunit Vaccine
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Mice
2.3. Preparations of Mtb Strains and Antigens
2.4. Immunisation and Mtb Infection in Mice
2.5. Intracellular Cytokine Staining
2.6. Bacterial Counts and Histopathological Analysis
2.7. Quantification of Cytokines
2.8. Cell Culture
2.9. In Vitro T-Cell Proliferation and Polarisation Assay
2.10. Colocalisation of Phagosomes and Phagolysosomes
2.11. Statistical Analysis
3. Results
3.1. Characterisation of the Immune Responses induced by HSP90-E6
3.2. HSP90-E6/CIA05 induces Ag-Specific Multifunctional T-Cells
3.3. Protective Efficacy of HSP90-E6 Boosting against Hypervirulent Mtb HN878
3.4. Multifunctional T-Cells and Cytokine Profiles in Mice Immunised with BCG Prime HSP90-E6/CIA05 Boosting after Challenge with Mtb HN878
3.5. Correlates of Protection for Improved BCG Boosting Efficacy of BCG-HSP90-E6/CIA05 in the Lungs
3.6. Th1- and Th17-Related Responses are Simultaneously induced in DCs and Co-Cultured CD4+ T-Cells upon Stimulation with HSP90-E6
3.7. IFN-γ and IL-17 Synergistically Exert Anti-Mycobacterial Activity Via Enhanced Phagolysosomal Maturation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Choi, H.-G.; Kwon, K.W.; Choi, S.; Back, Y.W.; Park, H.-S.; Kang, S.M.; Choi, E.; Shin, S.J.; Kim, H.-J. Antigen-Specific IFN-γ/IL-17-Co-Producing CD4+ T-Cells are the Determinants for Protective Efficacy of Tuberculosis Subunit Vaccine. Vaccines 2020, 8, 300. https://doi.org/10.3390/vaccines8020300
Choi H-G, Kwon KW, Choi S, Back YW, Park H-S, Kang SM, Choi E, Shin SJ, Kim H-J. Antigen-Specific IFN-γ/IL-17-Co-Producing CD4+ T-Cells are the Determinants for Protective Efficacy of Tuberculosis Subunit Vaccine. Vaccines. 2020; 8(2):300. https://doi.org/10.3390/vaccines8020300
Chicago/Turabian StyleChoi, Han-Gyu, Kee Woong Kwon, Seunga Choi, Yong Woo Back, Hye-Soo Park, Soon Myung Kang, Eunsol Choi, Sung Jae Shin, and Hwa-Jung Kim. 2020. "Antigen-Specific IFN-γ/IL-17-Co-Producing CD4+ T-Cells are the Determinants for Protective Efficacy of Tuberculosis Subunit Vaccine" Vaccines 8, no. 2: 300. https://doi.org/10.3390/vaccines8020300