A push-pull approach to maximize vaccine efficacy: Abrogating suppression with an IL-13 inhibitor while augmenting help with granulocyte/macrophage colony-stimulating factor and CD40L
Abstract
Although a role for CD4+ helper cells in CD8+ cytotoxic T lymphocyte (CTL) induction by vaccines is widely recognized, much less is known about a counterbalancing role of CD4+ T cells in down-modulating this response, or about ways to optimize vaccine responses through abrogation of this negative regulatory mechanism. Here, we discovered a synergistic enhancement of vaccine-mediated CTL induction and protection by the relief of suppression through depletion of regulatory CD4+ cells, including CD4+ NKT cells, or blockade of IL-13 made by these cells, combined with the cytokine granulocyte/macrophage colony-stimulating factor and the costimulatory molecule CD40L. Indeed, in the absence of helper epitopes, granulocyte/macrophage colony-stimulating factor and the helper-mimetic molecule CD40L are not sufficient to replace help to induce CTL without abrogation of CD4+ T cell-mediated suppression, suggesting a role for T cell help in overcoming suppression. The increased CTL induction translated to striking protection against viral infection by a vaccine by using this synergistic combined approach. These results argue for a push-pull approach to maximize vaccine efficacy, especially for HIV and cancer.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- October 2002
- DOI:
- 10.1073/pnas.192251199
- Bibcode:
- 2002PNAS...9913020A
- Keywords:
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- Immunology