| First Author | Stäger S | Year | 2006 |
| Journal | Eur J Immunol | Volume | 36 |
| Issue | 7 | Pages | 1764-71 |
| PubMed ID | 16791879 | Mgi Jnum | J:115789 |
| Mgi Id | MGI:3692204 | Doi | 10.1002/eji.200635937 |
| Citation | Stager S, et al. (2006) Distinct roles for IL-6 and IL-12p40 in mediating protection against Leishmania donovani and the expansion of IL-10+ CD4+ T cells. Eur J Immunol 36(7):1764-71 |
| abstractText | 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 (BMDC) 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. |
