| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Cellular Immunology, National Research Council-Institute for Biological Sciences, Ontario, Canada;
Institut National de la Santé et de la Recherche Médicale, Institut de Biologie, Campus Pasteur Lille, Lille, France; and
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ontario, Canada
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 (
7 days), resistant mice (129x1SvJ) harbor a chronic infection lasting 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 (CD62LhighIL-7R
highCD44high) CD8+ T cells. However, by day 14–21, majority of the primed CD8+ T cells display an effector phenotype (CD62LlowIL-7RlowCD44high). Subsequently, a progressive increase in the numbers of effector memory phenotype cells (CD62LlowIL-7RhighCD44high) 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.
This article has been cited by other articles:
|
|
 |
|
  S. Sad, R. Dudani, K. Gurnani, M. Russell, H. van Faassen, B. Finlay, and L. Krishnan Pathogen Proliferation Governs the Magnitude but Compromises the Function of CD8 T Cells J. Immunol., May 1, 2008; 180(9): 5853 - 5861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. M. van der Velden, J. T. Dougherty, and M. N. Starnbach Down-Modulation of TCR Expression by Salmonella enterica serovar Typhimurium J. Immunol., April 15, 2008; 180(8): 5569 - 5574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pejcic-Karapetrovic, K. Gurnani, M. S. Russell, B. B. Finlay, S. Sad, and L. Krishnan Pregnancy Impairs the Innate Immune Resistance to Salmonella typhimurium Leading to Rapid Fatal Infection J. Immunol., November 1, 2007; 179(9): 6088 - 6096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Russell, M. Iskandar, O. L. Mykytczuk, J. H. E. Nash, L. Krishnan, and S. Sad A Reduced Antigen Load In Vivo, Rather Than Weak Inflammation, Causes a Substantial Delay in CD8+ T Cell Priming against Mycobacterium bovis (Bacillus Calmette-Guerin) J. Immunol., July 1, 2007; 179(1): 211 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Jones-Carson, B. D. McCollister, E. T. Clambey, and A. Vazquez-Torres Systemic CD8 T-Cell Memory Response to a Salmonella Pathogenicity Island 2 Effector Is Restricted to Salmonella enterica Encountered in the Gastrointestinal Mucosa Infect. Immun., June 1, 2007; 75(6): 2708 - 2716. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
