Delayed expansion and contraction of CD8+ T cell response during infection with virulent Salmonella typhimurium.

Luu, Rachel A and Gurnani, Komal and Dudani, Renu and Kammara, Rajagopal and van Faassen, Henk and Sirard, Jean-Claude and Krishnan, Lakshmi and Sad, Subash (2006) Delayed expansion and contraction of CD8+ T cell response during infection with virulent Salmonella typhimurium. Journal of immunology (Baltimore, Md. : 1950), 177 (3). pp. 1516-25. ISSN 0022-1767

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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.

Item Type: Article
Additional Information: Copyright of this article belongs to American Association of Immunologists.
Subjects: Q Science > QR Microbiology > QR180 Immunology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 17 Feb 2012 16:47
Last Modified: 17 Feb 2012 16:47

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