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

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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 ofMHCclass 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. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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APA

Heit, A., Gebhardt, F., Lahl, K., Neuenhahn, M., Schmitz, F., Anderl, F., … Kastenmüller, K. (2008). Circumvention of regulatory CD4+ T cell activity during cross-priming strongly enhances T cell-mediated immunity. European Journal of Immunology, 38(6), 1585–1597. https://doi.org/10.1002/eji.200737966

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