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Journal ArticleDOI

Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells

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TLDR
The results illustrate that partially and sequen-tially induced (protective) immunity or complete exhaustion of T-cell immunity (high zone tolerance) are quantitatively different points on the scale of immunity; some viruses exploit the latter possibility to persist in an immunocompetent host.
Abstract
Viruses that are non- or poorly cytopathic have developed various strategies to avoid elimination by the immune system and to persist in the host. Acute infection of adult mice with the noncytopathic lymphocytic choriomeningitis virus (LCMV) normally induces a protective cytotoxic T-cell response that also causes immunopathology. But some LCMV strains (such as DOCILE (LCMV-D) or Cl-13 Armstrong (Cl-13)) derived from virus carrier mice tend to persist after acute infection of adult mice without causing lethal immunopathological disease. Tendency to persist correlates with tropism, rapidity of virus spread and virus mutations. We report here that these LCMV isolates may persist because they induce most of the specific antiviral CD8+ cytotoxic T cells so completely that they all disappear within a few days and therefore neither eliminate the virus nor cause lethal immunopathology. The results illustrate that partially and sequentially induced (protective) immunity or complete exhaustion of T-cell immunity (high zone tolerance) are quantitatively different points on the scale of immunity; some viruses exploit the latter possibility to persist in an immunocompetent host.

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Journal ArticleDOI

Tolerance, danger, and the extended family.

TL;DR: The possibility that the immune system does not care about self and non-self, that its primary driving force is the need to detect and protect against danger, and that it does not do the job alone, but receives positive and negative communications from an extended network of other bodily tissues is discussed.
Journal ArticleDOI

T cell exhaustion

TL;DR: Advances in the molecular delineation of T cell exhaustion are clarifying the underlying causes of this state of differentiation and also suggest promising therapeutic opportunities.
Journal ArticleDOI

Counting Antigen-Specific CD8 T Cells: A Reevaluation of Bystander Activation during Viral Infection

TL;DR: Much of the CD8 T cell expansion seen during viral infection represents antigen-specific cells and warrants a revision of current thinking on the size of the antiviral response.
Journal ArticleDOI

Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function

TL;DR: The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancingCD8 T cell immunity in chronically infected hosts.
Journal ArticleDOI

Lineage relationship and protective immunity of memory CD8 T cell subsets.

TL;DR: It is proposed that TCM and TEM do not necessarily represent distinct subsets, but are part of a continuum in a linear naive → effector → TEM → TCM differentiation pathway.
References
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Journal ArticleDOI

A cell culture model for T lymphocyte clonal anergy

TL;DR: The T cell enters an unresponsive state known as clonal anergy in which the T cell is incapable of producing its own growth hormone, interleukin-2, on restimulation.
Journal ArticleDOI

Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen

TL;DR: T-cell tolerance in transgenic mice expressing a T-cell receptor with double specificities for lymphocytic choriomeningitis virus (LCMV)-H-2Db and for the mixed-lymphocyte stimulatory (Mlsa) antigen is studied.
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Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals.

TL;DR: It is reported that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4- T cell death process, with the biochemical and ultrastructural features of apoptosis.
Journal ArticleDOI

Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity.

TL;DR: Evidence is presented that exposure of mature T cells to Mlsa antigens in vivo leads to specific tolerance and disappearance of MlsA-reactive V beta 6+ T cells, raising important questions concerning the relationship of tolerance and memory.
Journal ArticleDOI

Superantigens: Mechanism of T-Cell Stimulation and Role in Immune Responses

TL;DR: Studies that address the interactions between the foreign superantigens and MHC class-II molecules, the mechanism of T-cell stimulation, and the role that tolerance to self-superantigen plays in shaping the T- cell repertoire are reviewed.
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