Respiratory mucosal immunization with adenovirus gene transfer vector induces helper CD4 T cell-independent protective immunity.
BACKGROUND
Virus-vectored vaccine is a powerful activator of CD8 T cell-mediated immunity and is especially amenable to respiratory mucosal immunization, offering hopes for use in humans with diminished helper CD4 T cell function. However, whether virus-mediated mucosal immunization can produce immune protective CD8 T cells without the CD4 T cell help remains to be investigated.


METHODS
We used a replication-deficient adenovirus vector expressing an Mycobacterium tuberculosis antigen Ag85A for intranasal vaccination and evaluated its effect on CD8 T cell activation and protection in mice depleted of CD4 T cells.


RESULTS
Intranasal vaccination of CD4 T cell-depleted mice led to suboptimal generation of Ag-specific tetramer(+) or interferon (IFN)-gamma-producing CD8 T cells in the lung and spleen but this was observed mainly at the early time after vaccination. Reduced CD8 T cell priming was also accompanied by decreased CD8 T cell responses (CTL). Nevertheless, the ratio of Ag-specific CD8 T cells to IFN-gamma-producing CD8 T cells in CD4 T cell-depleted hosts remained comparable to that in CD4 T cell-competent hosts. Furthermore, the 'unhelped' CD8 T cells also displayed a similar immune phenotype as the 'helped' counterparts. The animals with 'unhelped' CD8 T cells were as well-protected from pulmonary M. tuberculosis challenge as those with 'helped' CD8 T cells in the absence of CD4 T cells.


CONCLUSIONS
The data obtained in the present study suggest that the fully immune protective CD8 T cells can still be generated by respiratory mucosal viral-mediated immunization without CD4 T cells and that CD8 T cells, 'helped' or 'unhelped', can confer significant protection against pulmonary tuberculosis independent of CD4 T cells.
Mu
Jingyu
J
Department of Pathology & Molecular Medicine, Centre for Gene Therapeutics & M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Jeyanathan
Mangalakumari
M
Shaler
Christopher R
CR
Horvath
Carly
C
Damjanovic
Daniela
D
Zganiacz
Anna
A
Kugathasan
Kapilan
K
McCormick
Sarah
S
Xing
Zhou
Z
D000217:Acyltransferases / Q000276:immunology / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005822:Genetic Vectors; D007114:Immunization; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D020545:Respiratory Mucosa / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology
D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis