Delayed expansion and contraction of CD8+ T cell response during infection with virulent Salmonella typhimurium.
Ag presentation to CD8(+) T cells often commences immediately after infection, which facilitates their rapid expansion and control of infection. Subsequently, the primed cells undergo rapid contraction. We report that this paradigm is not followed during infection with virulent Salmonella enterica, serovar Typhimurium (ST), an intracellular bacterium that replicates within phagosomes of infected cells. Although susceptible mice die rapidly (approximately 7 days), resistant mice (129 x 1SvJ) harbor a chronic infection lasting approximately 60-90 days. Using rOVA-expressing ST (ST-OVA), we show that T cell priming is considerably delayed in the resistant mice. CD8(+) T cells that are induced during ST-OVA infection undergo delayed expansion, which peaks around day 21, and is followed by protracted contraction. Initially, ST-OVA induces a small population of cycling central phenotype (CD62L(high)IL-7Ralpha(high)CD44(high)) CD8(+) T cells. However, by day 14-21, majority of the primed CD8(+) T cells display an effector phenotype (CD62L(low)IL-7Ralpha(low)CD44(high)). Subsequently, a progressive increase in the numbers of effector memory phenotype cells (CD62L(low)IL-7Ralpha(high)CD44(high)) occurs. This differentiation program remained unchanged after accelerated removal of the pathogen with antibiotics, as majority of the primed cells displayed an effector memory phenotype even at 6 mo postinfection. Despite the chronic infection, CD8(+) T cells induced by ST-OVA were functional as they exhibited killing ability and cytokine production. Importantly, even memory CD8(+) T cells failed to undergo rapid expansion in response to ST-OVA infection, suggesting a delay in T cell priming during infection with virulent ST-OVA. Thus, phagosomal lifestyle may allow escape from host CD8(+) T cell recognition, conferring a survival advantage to the pathogen.
Luu
Rachel A
RA
Laboratory of Cellular Immunology, National Research Council-Institute for Biological Sciences, Ontario, Canada.
Gurnani
Komal
K
Dudani
Renu
R
Kammara
Rajagopal
R
van Faassen
Henk
H
Sirard
Jean-Claude
JC
Krishnan
Lakshmi
L
Sad
Subash
S
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007156:Immunologic Memory; D016130:Immunophenotyping; D008089:Listeria monocytogenes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity*; D013997:Time Factors; D014774:Virulence
D018984:Epitopes, T-Lymphocyte; D010047:Ovalbumin