Tracking antigen-specific CD4+ T cells throughout the course of chronic Leishmania major infection in resistant mice

Antonio J. Pagán, Nathan C. Peters, Alain Debrabant, Flavia Ribeiro-Gomes, Marion Pepper, Christopher L. Karp, Marc Jenkins, David L. Sacks

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Primary Leishmania major infection typically produces cutaneous lesions that not only heal but also harbor persistent parasites. While the opposing roles of CD4+ T-cell-derived IFN-γ and IL-10 in promoting parasite killing and persistence have been well established, how these responses develop from naïve precursors has not been directly monitored throughout the course of infection. We used peptide:Major Histocompatibility Complex class II (pMHCII) tetramers to investigate the endogenous, parasite-specific primary CD4+ T-cell response to L. major in mice resistant to infection. Maximal frequencies of IFN-γ+ CD4+ T cells were observed in the spleen and infected ears within a month after infection and were maintained into the chronic phase. In contrast, peak frequencies of IL-10+ CD4+ T cells emerged within 2 weeks of infection, persisted into the chronic phase, and accumulated in the infected ears but not the spleen, via a process that depended on local antigen presentation. T helper type-1 (Th1) cells, not Foxp3+ regulatory T cells, were the chief producers of IL-10 and were not exhausted. Therefore, tracking antigen-specific CD4+ T cells revealed that IL-10 production by Th1 cells is not due to persistent T-cell antigen receptor stimulation, but rather driven by early antigen encounter at the site of infection.

Original languageEnglish (US)
Pages (from-to)427-438
Number of pages12
JournalEuropean Journal of Immunology
Volume43
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • CD4 T cells
  • IFN-γ
  • IL-10
  • Leishmania major
  • Tetramer

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