Role of B Cells in Mucosal Vaccine-Induced Protective CD8+ T Cell Immunity against Pulmonary Tuberculosis.
Emerging evidence suggests a role of B cells in host defense against primary pulmonary tuberculosis (TB). However, the role of B cells in TB vaccine-induced protective T cell immunity still remains unknown. Using a viral-vectored model TB vaccine and a number of experimental approaches, we have investigated the role of B cells in respiratory mucosal vaccine-induced T cell responses and protection against pulmonary TB. We found that respiratory mucosal vaccination activated Ag-specific B cell responses. Whereas respiratory mucosal vaccination elicited Ag-specific T cell responses in the airway and lung interstitium of genetic B cell-deficient (Jh(-/-) knockout [KO]) mice, the levels of airway T cell responses were lower than in wild-type hosts, which were associated with suboptimal protection against pulmonary Mycobacterium tuberculosis challenge. However, mucosal vaccination induced T cell responses in the airway and lung interstitium and protection in B cell-depleted wild-type mice to a similar extent as in B cell-competent hosts. Furthermore, by using an adoptive cell transfer approach, reconstitution of B cells in vaccinated Jh(-/-) KO mice did not enhance anti-TB protection. Moreover, respiratory mucosal vaccine-activated T cells alone were able to enhance anti-TB protection in SCID mice, and the transfer of vaccine-primed B cells alongside T cells did not further enhance such protection. Alternatively, adoptively transferring vaccine-primed T cells from Jh(-/-) KO mice into SCID mice only provided suboptimal protection. These data together suggest that B cells play a minimal role, and highlight a central role by T cells, in respiratory mucosal vaccine-induced protective immunity against M. tuberculosis.
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Amandeep K
AK
Khera
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Sam
S
Afkhami
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Rocky
R
Lai
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Mangalakumari
M
Jeyanathan
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Anna
A
Zganiacz
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Talveer
T
Mandur
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Joni
J
Hammill
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Daniela
D
Damjanovic
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada xingz@mcmaster.ca.
Zhou
Z
Xing
D000217:Acyltransferases / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination
D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis