title: Tracking antigen-specific CD8 T lymphocytes in the lungs of mice vaccinated with the Mtb72F polyprotein.
abstract: This study used a major histocompatibility complex class I tetramer reagent to track antigen-specific CD8 T cells in the lungs of mice immunized with the tuberculosis vaccine candidate Mtb72F. The results show that CD8 T cells recognizing an immunodominant Mtb32-specific epitope could be detected in significant numbers over the course of infection in mice exposed to low-dose aerosol challenge with Mycobacterium tuberculosis and that prior vaccination substantially increased the numbers of these cells early in the lungs. The effector phenotype of the cells was shown by the demonstration that many secreted gamma interferon, but very few contained granzyme B. As the course of the infection progressed, many activated CD8 T cells down-regulated expression of CD45RB and upregulated expression of the interleukin-7 receptor alpha chain, indicating a transition of these cells to a state of memory. These data support the hypothesis that M. tuberculosis-specific CD8 T cells can be targeted by vaccination with the Mtb72F polyprotein.
authors.affiliation: Mycobacterial Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523-1682, USA. sirwin@lamar.colostate.edu
authors.forename: Scott M
authors.initials: SM
authors.lastname: Irwin
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
authors.forename: Steven W
authors.initials: SW
authors.lastname: Dow
authors.forename: Y A W
authors.initials: YA
authors.lastname: Skeiky
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Mark R
authors.initials: MR
authors.lastname: Alderson
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D053804:Granzymes; D007371:Interferon-gamma / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D008081:Liposomes; D020395:Receptors, Interleukin-7; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases