Selective Depletion of Nonspecific T Cells During the Early Stage of Immune Responses to Infection

Jiang, Jiu; Lau, Lisa L.; Shen, Hao

doi:10.4049/jimmunol.171.8.4352

Cited by 111 publications

(126 citation statements)

References 29 publications

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“…Adoptively transferred cells in uninfected mice remained CFSE high and annexin V neg (data not shown). This is consistent with previously reported observations of selective depletion of T cells en masse via apoptosis in the spleens of mice infected with proinflammatory pathogens such as LM (30). Our results suggest that costimulation mediated via TNFR2 is important in rescuing Ag-specific T cells from generalized depletion that occurs during the early stages of LM infection.…”

Section: Cd8 T Cells Depend On Tnfr2 For Survival During the Early Phsupporting

confidence: 82%

TNF Receptor Type 2 (p75) Functions as a Costimulator for Antigen-Driven T Cell Responses In Vivo

Kim

Priatel

Teh

et al. 2006

The Journal of Immunology

142

130

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Naive T cells require costimulation for robust Ag-driven differentiation and survival. Members of the TNFR family have been shown to provide costimulatory signals conferring survival at distinct phases of the T cell response. In this study, we show that CD4 and CD8 T cells depend on TNFR type 2 (p75) for survival during clonal expansion, allowing larger accumulation of effector cells and conferring protection from apoptosis for a robust memory pool in vivo. We demonstrate using the MHC class I-restricted 2C TCR and MHC class II-restricted AND TCR transgenic systems that TNFR2 regulates the threshold for clonal expansion of CD4 and CD8 T cell subsets in response to cognate Ag. Using a novel recombinant Listeria monocytogenes (rLM) expressing a secreted form of the 2C agonist peptide (SIY) to investigate the role of TNFR2 for T cell immunity in vivo, we found that TNFR2 controls the survival and accumulation of effector cells during the primary response. TNFR2−/− CD8 T cells exhibit loss of protection from apoptosis that is correlated with diminished survivin and Bcl-2 expression. Null mutant mice were more susceptible to rLM-SIY challenge at high doses of primary infection, correlating with impaired LM-specific T cell response in the absence of TNFR2-mediated costimulation. Moreover, the resulting memory pools specific for SIY and listeriolysin O epitopes derived from rLM-SIY were diminished in TNFR2−/− mice. Thus, examination of Ag-driven T cell responses revealed a hitherto unknown costimulatory function for TNFR2 in regulating T cell survival during the differentiation program elicited by intracellular pathogen in vivo.

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Section: Cd8 T Cells Depend On Tnfr2 For Survival During the Early Phsupporting

confidence: 82%

TNF Receptor Type 2 (p75) Functions as a Costimulator for Antigen-Driven T Cell Responses In Vivo

Kim

Priatel

Teh

et al. 2006

The Journal of Immunology

142

130

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“…Consistent with this, a previous study has shown that nonspecific T cells are depleted early during infection with Listeria. 25 Our results show that rather than being depleted, CD8 lo cells expand in infected mice, suggesting that inflammatory cytokines produced in response to infection could promote the growth of these cells in vivo.…”

Section: Bystander Proliferation Of Cd8 Lo Cells In Response To Bactementioning

confidence: 79%

Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors

Dhanji

Teh

Oble

et al. 2004

Blood

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“…One possibility is that early proinflammatory signals, such as IFN-␣, could trigger physiological changes that do not lead to cell cycle progression, but that sensitize lymphocytes to the actions of LLO (23). It has been reported that there is early Ag-independent activation of CD8 ϩ lymphocytes during Listeria infection (24). Ag-nonspecific lymphocytes up-regulated CD69 by day 1 postinfection, but did not up-regulate late activation markers.…”

Section: Discussionmentioning

confidence: 99%

Listeriolysin O fromListeria monocytogenesIs a Lymphocyte Apoptogenic Molecule

Carrero

Calderon

Unanue

2004

The Journal of Immunology

134

146

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Infection of mice with Listeria monocytogenes caused marked lymphocyte apoptosis in the white pulp of the spleen on day 2 postinfection. We prove in this study that listeriolysin O (LLO), a pore-forming molecule and a major virulence factor of Listeria, could directly induce murine lymphocyte apoptosis both in vivo and in vitro at nanomolar and subnanomolar doses. Induction of apoptosis by LLO was rapid, with caspase activation seen as early as 30 min post-treatment. T cells lost their mitochondrial membrane potential and exposed phosphatidylserine within 8 h of treatment. Incubation of lymphocytes with a pan-caspase inhibitor blocked DNA laddering and caspase-3 activation, but did not block phosphatidylserine exposure or loss of mitochondrial membrane potential. We describe a novel function for LLO: induction of lymphocyte apoptosis with rapid kinetics, effected by both caspase-dependent and -independent pathways.

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Selective Depletion of Nonspecific T Cells During the Early Stage of Immune Responses to Infection

Cited by 111 publications

References 29 publications

TNF Receptor Type 2 (p75) Functions as a Costimulator for Antigen-Driven T Cell Responses In Vivo

TNF Receptor Type 2 (p75) Functions as a Costimulator for Antigen-Driven T Cell Responses In Vivo

Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors

Listeriolysin O fromListeria monocytogenesIs a Lymphocyte Apoptogenic Molecule

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