Dataset Information

The neurotrophic hepatocyte growth factor attenuates CD8+ cytotoxic T-lymphocyte activity.

ABSTRACT:

Background

Accumulating evidence suggests a deleterious role for CD8+ T cells in multiple sclerosis (MS) pathogenesis. We have recently reported that hepatocyte growth factor (HGF), a potent neuroprotective factor, limits CD4+ T cell-mediated autoimmune neuroinflammation by promoting tolerogenic dendritic cells (DCs) and subsequently regulatory T cells. Whether HGF modulates cell-mediated immunity driven by MHC class I-restricted CD8+ T cells remains to be determined.

Methods

Here we examined whether HGF regulates antigen-specific CD8+ T cell responses using an established model of murine cytotoxic T lymphocyte (CTL)-mediated killing.

Results

We found that HGF treatment of gp100-pulsed DCs reduced the activation of gp100-specific T cell receptor (Pmel-1) CD8+ T cells and subsequent MHC class I-restricted CTL-mediated cytolysis of gp100-pulsed target cells. The levels of perforin, granzyme B, IFN-?, and the degranulation marker CD107a as well as Fas ligand were decreased among CD8+ T cells, suggestive of a dual inhibitory effect of HGF on the perforin/granzyme B- and Fas-based lytic pathways in cell-mediated cytotoxicity. Treatment of CD8+ T cells with concanamycin A, a potent inhibitor of the perforin-mediated cytotoxic pathway, abrogated CTL cytotoxicity indicating that blockade of the perforin-dependent killing is a major mechanism by which HGF diminished cytolysis of gp100-pulsed target cells. Moreover, HGF suppressed the generation of effector memory CTLs.

Conclusions

Our findings indicate that HGF treatment limits both the generation and activity of effector CTL from naïve CD8+ T cells. Complementary to its impact on CD4+ T-cell CNS autoimmunity and myelin repair, our findings further suggest that HGF treatment could be exploited to control CD8+ T-cell-mediated, MHC I-restricted autoimmune dysfunctions such as MS.

SUBMITTER: Benkhoucha M

PROVIDER: S-EPMC3881506 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

The neurotrophic hepatocyte growth factor attenuates CD8+ cytotoxic T-lymphocyte activity.

Benkhoucha Mahdia M Molnarfi Nicolas N Schneiter Gregory G Walker Paul R PR Lalive Patrice H PH

Journal of neuroinflammation 20131217

<h4>Background</h4>Accumulating evidence suggests a deleterious role for CD8+ T cells in multiple sclerosis (MS) pathogenesis. We have recently reported that hepatocyte growth factor (HGF), a potent neuroprotective factor, limits CD4+ T cell-mediated autoimmune neuroinflammation by promoting tolerogenic dendritic cells (DCs) and subsequently regulatory T cells. Whether HGF modulates cell-mediated immunity driven by MHC class I-restricted CD8+ T cells remains to be determined.<h4>Methods</h4>Here ...[more]

PMID: 24344806

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Dataset Information

The neurotrophic hepatocyte growth factor attenuates CD8+ cytotoxic T-lymphocyte activity.

Background

Methods

Results

Conclusions

Publications

The neurotrophic hepatocyte growth factor attenuates CD8+ cytotoxic T-lymphocyte activity.

Similar Datasets

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