Prolonged antigen presentation, APC-, and CD8+ T cell turnover during mycobacterial infection: comparison with Listeria monocytogenes.
We expressed the CTL epitope of OVA (OVA(257-264)) in an acute (Listeria monocytogenes (LM)-OVA) and a chronic intracellular pathogen (Mycobacterium bovis (BCG)-OVA), to evaluate the kinetics of Ag presentation. LM-OVA proliferated rapidly in vivo, resulting in profound LM-OVA expansion within the first 24 h of infection, culminating in the generation of a potent CD8+ T cell response, which peaked on day 7 but underwent a rapid attrition subsequently. In contrast, BCG-OVA exhibited reduced growth in vivo, resulting in a delayed CD8+ T cell response that increased progressively with time. Relative to LM-OVA, BCG-OVA induced persistently increased numbers of apoptotic (annexin V+) CD8+ T cells. Ag presentation in vivo was evaluated by transferring Thy1.2+ carboxyfluorescein-labeled OT1 transgenic CD8+ T cells into infected Thy1.1+ congeneic recipient mice. LM-OVA induced rapid Ag presentation that was profound in magnitude, with most of the transferred cells getting activated within 4 days and resulting in a massive accumulation of activated donor CD8+ T cells. In contrast, Ag presentation induced by BCG-OVA was delayed, weaker in magnitude, which peaked around the second week of infection and declined to a low level subsequently. Increasing the dose of BCG-OVA while enhancing the magnitude of Ag presentation did not change the kinetics. Furthermore, a higher dose of BCG-OVA also accelerated the attrition of OVA(257-264)-specific CD8+ T cells. Relative to LM-OVA, the dendritic cells in BCG-OVA-infected mice were apoptotic for prolonged periods, suggesting that the rapid death of APCs may limit the magnitude of Ag presentation during chronic stages of mycobacterial infection.
van Faassen
Henk
H
Laboratory of Cellular Immunology, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
Dudani
Renu
R
Krishnan
Lakshmi
L
Sad
Subash
S
D000208:Acute Disease; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009164:Mycobacterium Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D010047:Ovalbumin