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IL-10 from Regulatory T Cells Determines Vaccine Efficacy in Murine Leishmania major Infection1

Summary: IL-10 from Regulatory T Cells Determines Vaccine Efficacy in
Murine Leishmania major Infection1
Carmel B. Stober,*
Uta G. Lange,*
Mark T. M. Roberts,*
Antonio Alcami,
Jenefer M. Blackwell2
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- 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- 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- :IL-10 was thus a clear prechallenge indicator of vaccine
success. Challenge infection caused further polarization to high IL-10/low IFN- with LACK and low IL-10/high IFN- 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


Source: Arnold, Jonathan - Nanoscale Science and Engineering Center & Department of Genetics, University of Georgia


Collections: Biotechnology