Fms-Like Tyrosine Kinase 3-Based Immunoprophylaxis against Infection Is Improved by Adjuvant Treatment with Anti-Interleukin-10 Antibody.

摘要

Background. Fms-like tyrosine kinase 3 ligand (Flt3L) expands dendritic-cell populations in vivo and protects against microbial infection in healthy and immunocompromised hosts. Approaches for optimizing the protective effects of Flt3L in vivo are not well known.Methods. BALB/c mice were treated for 9 days with 10 mu g of recombinant (r) Flt3L with or without the addition of 250 mu g of anti-interleukin (IL)-10 antibody on day 9. After Leishmania major infection, disease progression was determined by measuring cutaneous lesions. Production of IL-12 and interferon (IFN)- gamma were determined.Results. Flt3L pretreatment increased the synthesis of CD40-inducible IL-12 p40 but not of bioactive p70. Coculture with anti-IL-10 antibody increased p70 production. Combined Flt3L and single-dose anti-IL-10 antibody pretreatment improved lesion cure rates from 40% to 87% relative to mice pretreated with rFlt3L only (P<.01, chi (2) test) and increased T helper 1 (Th1)-type cytokine production 4 weeks after infection but did not cure Rag-2- and IFN- gamma -knockout BALB/c mice. Flt3L and anti-IL-10 antibody pretreatments increased frequencies of IL-12- and IFN- gamma -secreting cells 2 and 4 days after infection. Both natural killer and CD4(+) cells contributed to increased early IFN- gamma production.Conclusion. A single dose of anti-IL-10 antibody significantly improves Flt3L immunoprophylaxis against infection mediated by Th1-type adaptive responses.