CD8+ CTL from lungs of Mycobacterium tuberculosis-infected mice express perforin in vivo and lyse infected macrophages.
CD8+ T lymphocytes have been implicated in the protective immune response against human and murine tuberculosis. However, the functional role that this cell subset plays during the resolution of infection remains controversial. In this study, we demonstrate the presence of Mycobacterium tuberculosis-specific CD8+ CTL in the lungs and lung-draining lymph nodes of mice infected with M. tuberculosis via the aerosol or i.v. route. These cells expressed perforin in vivo and specifically recognized and lysed M. tuberculosis-infected macrophages in a perforin-dependent manner after a short period of in vitro restimulation. The efficiency of lysis of infected macrophages was dependent upon the time allowed for interaction between macrophage and M. tuberculosis bacilli. Recognition of infected targets by CD8+ CTL was beta 2-microglobulin and MHC class I dependent and was not CD1d restricted. The presented data indicate that CD8+ T cells contribute to the protective immune response during M. tuberculosis infection by exerting cytotoxic function and lysing infected macrophages.
Serbina
N V
NV
Departments of Molecular Genetics and Biochemistry and Medicine, and University of Pittsburgh School of Medicine, PA 15261, USA.
Liu
C C
CC
Scanga
C A
CA
Flynn
J L
JL
D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009928:Organ Specificity / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D000336:Aerosols; D000942:Antigens, Bacterial; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D001613:beta 2-Microglobulin; D054353:Perforin