Leishmania-infected macrophages sequester endogenously synthesized parasite antigens from presentation to CD4+ T cells

Peter E. Kima, Lynn Soong, Carmen Chicharro, Nancy H. Ruddle, Diane McMahon-Pratt

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

CD4+ T cell lines raised against the protective leishmanial antigens GP46 and P8 were used to study the presentation of endogenously synthesized Leishmania antigens by infected cells. Using two different sources of macrophages, the I4.07 macrophage cell line (H-2(k)) which constitutively expresses major histocompatibility complex (MHC) class II molecules, and elicited peritoneal exudate cells, we found that cells infected with Leishmania amastigotes presented little, if any endogenously synthesized parasite antigens to CD4+ T cells. In contrast, promastigote-infected macrophages did present endogenous parasite molecules to CD4+ T cells, although only for a limited time, with maximal presentation occurring within 24 h of infection and decreasing to minimal antigen presentation at 72 h post-infection. These observations suggest that once within the macrophage. Leishmania amastigote antigens are sequestered from the MHC class II pathway of antigen presentation. This allows live parasites to persist in infected hosts by evading the activation of CD4+ T cells, a major and critical anti-leishmanial component of the host immune system. Studies with drugs that modify fusion patterns of phagosomes suggest that the mechanism of this antigen sequestration includes targeted fusion of the parasitophorous vacuole with certain endocytic compartments.

Original languageEnglish (US)
Pages (from-to)3163-3169
Number of pages7
JournalEuropean Journal of Immunology
Volume26
Issue number12
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Antigen presentation
  • CD4 T cell
  • Leishmania
  • Macrophage

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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