Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

Abstract

Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

DOI: 10.1002/eji.200737966

Cite this paper

@article{Heit2008CircumventionOR, title={Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.}, author={Antje Heit and Friedemann E Gebhardt and Katharina Lahl and Michael Neuenhahn and Frank Schmitz and Florian Anderl and Hermann Wagner and Tim Sparwasser and Dirk H Busch and Kathrin Kastenmueller}, journal={European journal of immunology}, year={2008}, volume={38 6}, pages={1585-97} }