Duration of Infection and Antigen Display Have Minimal Influence on the Kinetics of the CD4+ T Cell Response to <i>Listeria monocytogenes</i> Infection

Corbin, Gail A.; Harty, John T.

doi:10.4049/jimmunol.173.9.5679

Cited by 94 publications

(105 citation statements)

References 67 publications

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“…We have now shown that activated IFN-␥ receptor KO CD4 ϩ T cells did not undergo increased apoptosis even when transferred into WT mice, where the BCG growth is under immunological control. In a different study, the duration of infection and Ag display during Listeria infection had a minimal effect on the expansion and contraction of CD4 ϩ T cells (43). Similarly, during infection with attenuated Listeria, the Agspecific CD4…”

Section: Discussionmentioning

confidence: 99%

IFN-γ Acts Directly on Activated CD4+ T Cells during Mycobacterial Infection to Promote Apoptosis by Inducing Components of the Intracellular Apoptosis Machinery and by Inducing Extracellular Proapoptotic Signals

McKinstry

Swain

et al. 2007

The Journal of Immunology

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Despite many studies, the regulation of CD4+ T cell apoptosis during the shutdown of immune responses is not fully understood. We have investigated the molecular mechanisms of IFN-γ in regulating apoptosis of CD4+ T cells during bacillus Calmette-Guérin (BCG) infection of mice. Our data provide new insight into the regulation of CD4+ T cell apoptosis by IFN-γ. As CD4+ T cells responded to BCG infection, there was a coordinated increase in IFN-γ production by effector CD4+ T cells and a coordinated IFN-γ-dependent up-regulation of many diverse apoptosis-pathway genes in effector CD4+ T cells. Unexpectedly, IFN-γ up-regulated transcripts and protein expression of Bcl-2, Bax, Bim, Bid, Apaf-1, and caspase-9 in activated CD4+ T cells—components of the apoptosis machinery that are involved in promoting mitochondrial damage-mediated apoptosis. Wild-type, but not IFN-γ knockout, CD4+ T cells underwent apoptosis that was associated with damaged mitochondrial membranes. IFN-γ also up-regulated expression of cell-extrinsic signals of apoptosis, including TRAIL, DR5, and TNFR1. Cell-extrinsic apoptosis signals from TNF-α, TRAIL, and NO were capable of damaging the mitochondrial membranes in activated CD4+ T cells. Moreover, activated CD4+ T cells from BCG-infected DR5, TNFR1, and inducible NO synthase knockout mice had impaired caspase-9 activity, suggesting impaired mitochondria-pathway apoptosis. We propose that IFN-γ promotes apoptosis of CD4+ T cells during BCG infection as follows: 1) by sensitizing CD4+ T cells to apoptosis by inducing intracellular apoptosis molecules and 2) by inducing cell-extrinsic apoptosis signals that kill CD4+ effector T cells.

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Section: Discussionmentioning

confidence: 99%

IFN-γ Acts Directly on Activated CD4+ T Cells during Mycobacterial Infection to Promote Apoptosis by Inducing Components of the Intracellular Apoptosis Machinery and by Inducing Extracellular Proapoptotic Signals

McKinstry

Swain

et al. 2007

The Journal of Immunology

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“…As these populations of cells expand during the immune response, they begin to become detectable four to five days post-L. monocytogenes infection. The primary T cell response peaks seven to nine days post-infection [65] and the extent of this proliferation and differentiation is independent of antigen [66][67][68]. The population of antigen-specific T cells then contracts to a smaller population of stable memory T cells.…”

Section: Cd4 and Cd8 T Cell Responsesmentioning

confidence: 99%

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

Zenewicz

Shen

2007

Microbes and Infection

177

172

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The Gram-positive facultative intracellular bacterium Listeria monocytogenes is a model pathogen for elucidating important mechanisms of the immune response. Infection of mice with a sub-lethal dose of bacteria generates highly reproducible innate and adaptive immune responses, resulting in clearance of the bacteria and resistance to subsequent L. monocytogenes infection. Both the innate and adaptive immune systems are crucial to the recognition and elimination of this pathogen from the host.

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“…In apparent contrast to CD8 T cells, naive CD4 T cells are believed to require longer periods of stimulation to initiate proliferation (5-7) and differentiation into effector cells (8,9). Additionally, in vivo studies indicate that shortening the length of Listeria monocytogenes infection by antibiotic treatment can affect CD4 T cell activation and development of memory T cells, but this effect is dependent on infectious dose, suggesting that overall antigen levels may play a role (10,11). Thus, divergent mechanisms seem to regulate the differentiation of CD4 and CD8 T cells.…”

mentioning

confidence: 99%

Increased competition for antigen during priming negatively impacts the generation of memory CD4 T cells

Blair

Lefrançois

2007

Proc. Natl. Acad. Sci. U.S.A.

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The factors involved in the differentiation of memory CD4 T cells from naïve precursors are poorly understood. We developed a system to examine the effect of increased competition for antigen by CD4 T cells on the generation of memory in response to infection with a recombinant vesicular stomatitis virus. Competition was initially regulated by increasing the precursor frequency of adoptively transferred naïve T cell antigen receptor transgenic CD4 T cells. Despite robust proliferation at high precursor frequencies, memory CD4 T cells did not develop, whereas decreasing the input number of naïve CD4 T cells promoted memory development after infection. The lack of memory development was linked to reduced blastogenesis and poor effector cell induction, but not to initial recruitment or proliferation of antigen-specific CD4 T cells. To prove that availability of antigen alone could regulate memory CD4 T cell development, we used treatment with an mAb specific for the epitope recognized by the transferred CD4 T cells. At high doses, this mAb effectively inhibited the antigen-specific CD4 T cell response. However, at a very low dose of mAb, primary CD4 T cell expansion was unaffected, although memory development was dramatically reduced. Moreover, the induction of effector function was concomitantly inhibited. Thus, competition for antigen during CD4 T cell priming is a major contributing factor to the development of the memory CD4 T cell pool.infection ͉ effector ͉ differentiation ͉ precursor frequency

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Duration of Infection and Antigen Display Have Minimal Influence on the Kinetics of the CD4+ T Cell Response to Listeria monocytogenes Infection

Cited by 94 publications

References 67 publications

IFN-γ Acts Directly on Activated CD4+ T Cells during Mycobacterial Infection to Promote Apoptosis by Inducing Components of the Intracellular Apoptosis Machinery and by Inducing Extracellular Proapoptotic Signals

IFN-γ Acts Directly on Activated CD4+ T Cells during Mycobacterial Infection to Promote Apoptosis by Inducing Components of the Intracellular Apoptosis Machinery and by Inducing Extracellular Proapoptotic Signals

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

Increased competition for antigen during priming negatively impacts the generation of memory CD4 T cells

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