T Cell Responses to Viral Infections: Lessons from Lymphocytic Choriomeningitis Virus

Khanolkar, Aaruni; Fuller, Michael J.; Zajac, Allan

doi:10.1385/ir:26:1-3:309

Cited by 46 publications

(43 citation statements)

References 49 publications

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“…6), become CD44 int ( Fig. 2F) (39), are predominately CD69 high (20), and tend to remain CD62L low (30,59) before becoming physically deleted. This expression profile indicates that Ag-specific T cells remain activated despite their inability to elaborate effector activities.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we have used the well-defined system of lymphocytic choriomeningitis virus (LCMV) 3 infection of mice to determine quantitative and qualitative changes in virus-specific CD8 T cell responses that rapidly resolve acute infection, more slowly control protracted infection, or that fail to clear chronic infection (30). We document that protracted and chronic infections result in the step-wise inactivation of virus-specific CD8 T cell responses; however, if viral loads can be brought under control, functionally competent CD8 T cells reemerge.…”

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confidence: 99%

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Maintenance, Loss, and Resurgence of T Cell Responses During Acute, Protracted, and Chronic Viral Infections

Fuller

Khanolkar

Tebo

et al. 2004

The Journal of Immunology

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199

248

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The acute phase of many viral infections is associated with the induction of a pronounced CD8 T cell response which plays a principle role in clearing the infection. By contrast, certain infections are not as readily controlled. In this study, we have used the well-defined system of lymphocytic choriomeningitis virus (LCMV) infection of mice to determine quantitative and qualitative changes in virus-specific CD8 T cell responses that rapidly resolve acute infections, more slowly control protracted infections, or fail to clear chronic infections. Acute LCMV infection elicits potent, functional, multi-epitope-specific CD8 T cell responses. Virus-specific CD8 T cells also expand, albeit to a lesser extent, during protracted LCMV infection. Under these conditions, there is a progressive diminution in the capacity to produce IL-2, TNF-α, and IFN-γ. Changes in cytotoxic activities are also detectable but differ depending upon the specificity of the responding cells. As the infection is slowly resolved, a resurgence of cytokine production by virus-specific CD8 T cells is observed. CD4-deficient mice cannot control infection with certain strains of LCMV, but do mount multi-epitope-specific CD8 T cell responses that also lose effector capabilities; however, they are not maintained indefinitely in an unresponsive state as these cells become deleted over time. Overall, our findings suggest that constant high viral loads result in the progressive diminution of T cell effector functions and subsequent physical loss of the responding cells, whereas if the viral load is brought under control a partial restoration of CD8 T cell functions can occur.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Maintenance, Loss, and Resurgence of T Cell Responses During Acute, Protracted, and Chronic Viral Infections

Fuller

Khanolkar

Tebo

et al. 2004

The Journal of Immunology

Self Cite

199

248

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“…Early during infection, STIM1 and STIM2 were required for the differentiation of naive CD8 + T cells into fully functional cytolytic effector cells and mediated the production of cytokines and prevented cellular exhaustion in viral-specific CD8 + effector T cells. [33][34][35][36][37][38][39][40][41] . The total numbers of NP 396-404 -and GP [33][34][35][36][37][38][39][40][41] -specific CD8 + T cells were comparable in DKO and WT mice 8 and 35 days p.i., but were moderately reduced 60 days p.i.…”

Section: +mentioning

confidence: 99%

CD4+ and CD8+ T cell–dependent antiviral immunity requires STIM1 and STIM2

Shaw¹,

Weidinger²,

Vaeth³

et al. 2014

J. Clin. Invest.

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“…What is understood about T cell responses to microbial pathogens is largely based on work done using model pathogens such as Listeria monocytogenes and lymphocytic choriomeningitis virus (6,(12)(13)(14)(15)(16)(17). However, as investigators have explored T cell responses to other microbial pathogens, it has become clear that these T cell responses can differ greatly from those seen following infection with model pathogens.…”

mentioning

confidence: 99%

Down-Modulation of TCR Expression by Salmonella enterica serovar Typhimurium

Velden

Dougherty

Starnbach

2008

The Journal of Immunology

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T cell-mediated adaptive immunity is required to help clear infection with the facultative intracellular bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), yet development of T cell-mediated adaptive immunity to S. Typhimurium has been described as slow and inefficient. A key step in inducing T cell-mediated adaptive immunity is T cell priming; the activation, proliferation, and differentiation of naive T cells following initial encounter with Ag. We previously demonstrated that S. Typhimurium had a direct inhibitory effect on naive T cells from mouse, blocking their proliferation. In this study, we show that S. Typhimurium down-modulates expression of the TCR β-chain, a molecule that is essential for Ag recognition and T cell function. Specifically, we demonstrate that reduced amounts of surface and intracellular TCR-β protein and decreased levels of tcrβ transcript are expressed by T cells cultured in the presence of S. Typhimurium. We further show that the down-modulation of TCR-β expression requires contact between S. Typhimurium and the T cells and that once contact occurs, a factor capable of reducing TCR-β expression is secreted. These results provide new insight into the mechanism by which S. Typhimurium may inhibit T cell priming and avoid clearance by the adaptive immune system.

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T Cell Responses to Viral Infections: Lessons from Lymphocytic Choriomeningitis Virus

Cited by 46 publications

References 49 publications

Maintenance, Loss, and Resurgence of T Cell Responses During Acute, Protracted, and Chronic Viral Infections

Maintenance, Loss, and Resurgence of T Cell Responses During Acute, Protracted, and Chronic Viral Infections

CD4+ and CD8+ T cell–dependent antiviral immunity requires STIM1 and STIM2

Down-Modulation of TCR Expression by Salmonella enterica serovar Typhimurium

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