Differentiation of monocytic cell clones into CD8 alpha+ dendritic cells (DC) suggests that monocytes can be direct precursors for both CD8 alpha+ and CD8 alpha- DC in the mouse

J Immunol. 2003 Jun 15;170(12):5927-35. doi: 10.4049/jimmunol.170.12.5927.

Abstract

Dendritic cells (DC) are the professional APCs that initiate T cell immune responses. DC can develop from both myeloid and lymphoid progenitors. In the mouse, the CD8alpha(+) DC had been designated as "lymphoid" DC, and CD8alpha(-) DC as "myeloid" DC until recently when it was demonstrated that common myeloid progenitors can also give rise to CD8alpha(+) DC in bone marrow chimera mice. However, it is still not clear which committed myeloid lineages differentiate into CD8alpha(+) DC. Because monocytes can differentiate into DC in vivo, the simplest hypothesis is that the CD8alpha(+) DC can be derived from the monocyte/macrophage. In this study we show that cell clones, isolated from CD8alpha(+) DC lymphoma but with a monocytic phenotype (CD11c(low/-)D11b(high)CD8alpha(-)I-A(low)), can redifferentiate into CD8alpha(+) DC either when stimulated by LPS and CD40L or when they migrate into the lymphoid organs. Maturation of DC in vivo correlated with strong priming of allogeneic T cells. Moreover, the monocytes from cultured splenocytes or peritoneal exudates macrophages of wild-type mice are also capable of differentiating into CD11c(+)CD8alpha(+) DC after their migration into the draining lymph nodes. Our results suggest that monocytes can be direct precursors for CD11c(+)CD8alpha(+) DC in vivo. In addition, the monocyte clones described in this study may be valuable for studying the differentiation and function of CD8alpha(+) DC that mediate cross-presentation of Ag to CD8 T cells specific for cell-associate Ags.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Adoptive Transfer
  • Animals
  • CD8 Antigens / biosynthesis*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Separation
  • Clone Cells
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • H-2 Antigens / immunology
  • Histocompatibility Antigen H-2D
  • Immunization
  • Injections, Subcutaneous
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphoma / genetics
  • Lymphoma / immunology
  • Lymphoma / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / cytology*
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / transplantation
  • Neoplasm Transplantation
  • STAT1 Transcription Factor
  • Stem Cells / cytology*
  • Stem Cells / immunology*
  • Stem Cells / metabolism
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics

Substances

  • CD8 Antigens
  • CD8alpha antigen
  • DNA-Binding Proteins
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Trans-Activators
  • Tumor Suppressor Protein p53