CD169+ macrophages are sufficient for priming of CTLs with specificities left out by cross-priming dendritic cells

Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5461-6. doi: 10.1073/pnas.1423356112. Epub 2015 Apr 14.

Abstract

Dendritic cells (DCs) are considered the most potent antigen-presenting cells (APCs), which directly prime or cross-prime MHC I-restricted cytotoxic T cells (CTLs). However, recent evidence suggests the existence of other, as-yet unidentified APCs also able to prime T cells. To identify those APCs, we used adenoviral (rAd) vectors, which do not infect DCs but selectively accumulate in CD169(+) macrophages (MPs). In mice that lack DCs, infection of CD169(+) MPs was sufficient to prime CTLs specific for all epitopes tested. In contrast, CTL responses relying exclusively on cross-presenting DCs were biased to selected strong MHC I-binding peptides only. When both DCs and MPs were absent, no CTL responses could be elicited. Therefore, CD169(+) MPs can be considered APCs that significantly contribute to CTL responses.

Keywords: CD169+ macrophage; CD8 T cell; adenovirus; cross-presentation; dendritic cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / physiology*
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cross Reactions / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • Lectins, C-Type / immunology*
  • Mice

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Epitopes, T-Lymphocyte
  • Lectins, C-Type