IL-10 from Regulatory T Cells Determines Vaccine Efficacy in Murine Leishmania major Infection
| العنوان: | IL-10 from Regulatory T Cells Determines Vaccine Efficacy in Murine Leishmania major Infection |
|---|---|
| المؤلفون: | Uta G. Lange, Jenefer M. Blackwell, Carmel B. Stober, Mark Roberts, Antonio Alcami |
| المصدر: | The Journal of Immunology. 175:2517-2524 |
| بيانات النشر: | The American Association of Immunologists, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Protozoan Vaccines, Immunology, Immunization, Secondary, Protozoan Proteins, Leishmaniasis, Cutaneous, Antigens, Protozoan, Vaccinia virus, Biology, T-Lymphocytes, Regulatory, Interferon-gamma, Mice, chemistry.chemical_compound, Antigen, Predictive Value of Tests, Immunity, Vaccines, DNA, Animals, Immunology and Allergy, Leishmania major, Treatment Failure, IL-2 receptor, Mice, Inbred BALB C, Receptors, Interleukin-2, Vaccine efficacy, biology.organism_classification, Virology, Interleukin-10, Interleukin 10, Immunity, Active, Peroxidases, chemistry, Immunoglobulin G, Female, Interleukin-4, Vaccinia, Vaccine failure |
| الوصف: | Leishmaniasis affects 12 million people, but there are no vaccines. Immunological correlates of vaccine efficacy are unclear. Polarized Th1 vs Th2 responses in Leishmania major-infected mice suggested that a shift in balance from IL-4 to IFN-γ was the key to vaccine success. Recently, a role for IL-10 and regulatory T cells in parasite persistence was demonstrated, prompting re-evaluation of vaccine-induced immunity. We compared DNA/modified vaccinia virus Ankara heterologous prime-boost with Leishmania homolog of the receptor for activated C kinase (LACK) or tryparedoxin peroxidase (TRYP). Both induced low IL-4 and high IFN-γ prechallenge. Strikingly, high prechallenge CD4 T cell-derived IL-10 predicted vaccine failure using LACK, whereas low IL-10 predicted protection with TRYP. The ratio of IFN-γ:IL-10 was thus a clear prechallenge indicator of vaccine success. Challenge infection caused further polarization to high IL-10/low IFN-γ with LACK and low IL-10/high IFN-γ with TRYP. Ex vivo quantitative RT-PCR and in vitro depletion and suppression experiments demonstrated that Ag-driven CD4+CD25+ T regulatory 1-like cells were the primary source of IL-10 in LACK-vaccinated mice. Anti-IL-10R treatment in vivo demonstrated that IL-10 was functional in determining vaccine failure, rendering LACK protective in the presence of high IFN-γ/low IL-5 responses. |
| تدمد: | 1550-6606 0022-1767 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f973d191e26212f53279098735a0e56 https://doi.org/10.4049/jimmunol.175.4.2517 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0f973d191e26212f53279098735a0e56 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
|---|