IL-10 production differentially influences the magnitude, quality, and protective capacity of Th1 responses depending on the vaccine platform

Patricia A. Darrah, Sonia T. Hegde, Dipti T. Patel, Ross W.B. Lindsay, Linda Chen, Mario Roederer, Robert A. Seder

Research output: Contribution to journalArticlepeer-review

Abstract

The quality of a Th1 response can be a prospective correlate of vaccine-mediated protection against certain intracellular pathogens. Using two distinct vaccine platforms, we evaluate the influence of interleukin (IL) 10 production on the magnitude, quality, and protective capacity of CD4+ T cell responses in the mouse model of Leishmania major infection. Multiparameter flow cytometry was used to delineate the CD4+ T cell production of interferon (IFN) γ, IL-2, tumor necrosis factor (TNF), and IL-10 (or combinations thereof) after vaccination. Immunization with a high dose of adenovirus (ADV) expressing leishmanial proteins (MML-ADV) elicited a limited proportion of multifunctional IFN-γ+ IL-2 +TNF+ Th1 cells, a high frequency of IL-10-producing CD4+ T cells, and did not protect against subsequent challenge. Surprisingly, in the absence of IL-10, there was no change in the magnitude, quality, or protective capacity of the Th1 response elicited by high-dose MML-ADV. In contrast, after immunization with MML protein and CpG (MML + CpG), IL-10 limited the production of IL-12 by DCs in vivo, thereby decreasing the generation of multifunctional Th1 cells. Consequently, three immunizations with MML + CpG were required for full protection. However, inhibiting IL-10 at the time of immunization enhanced the magnitude and quality of the Th1 response sufficiently to mediate protection after only a single immunization. Overall, we delineate distinct mechanisms by which vaccines elicit protective Th1 responses and underscore the importance of multifunctional CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)1421-1433
Number of pages13
JournalJournal of Experimental Medicine
Volume207
Issue number7
DOIs
StatePublished - Jul 5 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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