CD8- and CD95/95L-dependent mechanisms of resistance in mice with chronic pulmonary tuberculosis.
The role of CD8 T lymphocytes in the immune response to Mycobacterium tuberculosis infection remains enigmatic, with persuasive reports of both cytolytic and noncytolytic (cytokine-mediated) responses to infection. To address the importance of the cytolytic mechanisms, mice with targeted disruptions for CD8 and perforin or with gene mutations in the CD95/ CD95L signaling pathway were exposed to pulmonary infection. All mice tested showed no differences in their ability to contain the growth of infection during the early phase of disease. As the chronic phase of the disease ensued, however, both CD8- and CD95/CD95L-deficient mice gradually lost their ability to limit bacterial growth. This was associated with a tendency toward pyogenic inflammation in the lung. This tendency was not seen in the perforin gene-disrupted mice. In CD8 gene-disrupted mice, the ability to generate interferon-gamma secreting T cells was unimpaired. Although these cells were capable of entering the lung they were unable to influence the increasing bacterial load in this organ.
Turner
J
J
Mycobacterial Research Laboratories, Colorado State University, 200 W. Lake, Fort Collins, CO 80523, USA.
D'Souza
C D
CD
Pearl
J E
JE
Marietta
P
P
Noel
M
M
Frank
A A
AA
Appelberg
R
R
Orme
I M
IM
Cooper
A M
AM
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000032:analysis; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D015704:CD4 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D007371:Interferon-gamma