H2‐M3‐restricted CD8+ T cells augment CD4+ T‐cell responses by promoting DC maturation |
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Authors: | Michael T Chow Hung‐Sia Teh |
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Institution: | Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada |
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Abstract: | Infection with Listeria monocytogenes triggers the activation and expansion of nonconventional CD8+ T cells restricted by the MHC class Ib molecule, H2‐M3. H2‐M3‐restricted CD8+ T cells exhibit a memory phenotype, rapidly produce cytokines, and reach peak frequencies sooner than conventional MHC class Ia‐restricted CD8+ T cells. In this study, we found that simultaneous in vivo priming of H2‐M3‐restricted T cells and adoptively transferred OT‐II CD4+ T cells on the same DC enhances the survival of OT‐II cells. Stimulation of H2‐M3‐restricted T cells were found to induce DC maturation resulting in costimulatory molecule upregulation and production of TH1‐type cytokines, which was dependent on both cell‐to‐cell contact and soluble factors, particularly TNF‐α, produced by activated H2‐M3‐restricted T cells. Interestingly, H2‐M3‐restricted T cells were more efficient than activated NK cells in inducing DC maturation. Furthermore, we found that OVA323–339‐coated DC matured by coculturing with peptide‐stimulated H2‐M3‐restricted T cells were more efficient in stimulating the proliferation of Ag‐activated OT‐II cells. This study indicates that H2‐M3‐restricted T cells promote immune responses by CD4+ T cells by inducing DC maturation and suggests novel mechanisms for vaccine development. |
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Keywords: | Adjuvants CD8+ T cells DC Innate immunity MHC class Ib molecules |
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