期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 36, 期 7, 页码 1764-1771出版社
WILEY
DOI: 10.1002/eji.200635937
关键词
cytokines; dendritic cells; immunotherapy; Leishmania
类别
资金
- Medical Research Council [G0400786(71636), G0400786] Funding Source: Medline
- Wellcome Trust [065308] Funding Source: Medline
- Medical Research Council [G0400786] Funding Source: researchfish
- MRC [G0400786] Funding Source: UKRI
Adoptive dendritic cell (DC) immunotherapy provides a useful experimental tool to evaluate immunoregulation in vivo and has previously been successfully used to enhance host resistance in a variety of experimental models of leishmaniasis. Here, we used this approach to identify IL-6 and IL-12p40 as critical cytokines that cooperate to mediate host protection to Leishmania donovani but which act independently to regulate expansion of IL-10(+) CD4(+) T cells, shown here for the first time to be associated with this infection. Adoptive transfer of LPS-activated bone marrow-derived DC (BMDQ from wild-type mice was therapeutically beneficial and led to enhanced resistance as measured by spleen parasite burden. In contrast, IL-6- or IL-12p40-deficient BMDC had no protective benefit, indicating that production of both cytokines was essential for the therapeutic efficacy of DC. IL-10 production by CD25(-) FoxP3(-) IL-10(+) CD4(+) T cells is a strong correlate of disease progression, and BMDC from wild-type mice inhibited expansion of these cells. Strikingly, IL-12-deficient BMDC could also inhibit the expansion of this T cell population whereas IL-6-deficient BMDC could not, indicating that IL-6 played a key role in this aspect of DC function in vivo. Breadth of cytokine production is thus an important factor when considering strategies for DC-based interventions.
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