Human dendritic cells and transplant outcome

Abstract

Early interest in dendritic cells (DC) in transplantation centered on the role of graft interstitial DC in the instigation of rejection. Much information has subsequently accumulated concerning the phenotypic and functional diversity of these rare, migratory, bone marrow-derived antigen-presenting cells, and their role in the induction and regulation of immunity. Detailed insights have emerged from studies of freshly isolated or in vitro-propagated DC, and from analyses of their function in experimental animal models. The functional plasticity of these uniquely well-equipped antigen-presenting cells is reflected in their ability not only to induce alloimmune responses, but also to serve as potential targets and therapeutic agents for the long-term improvement of transplant outcome. Notably, however, a great deal remains to be understood about the immunobiology of DC populations in relation to human transplant outcome. Herein, we briefly review aspects of human DC biology in organ and bone marrow transplantation, the potential of these cells for monitoring outcome, and the role of DC in development of vaccines to protect against infectious disease or to promote allograft tolerance.

FIGURE 1

Strategies used for the identification of circulating human DC subset precursors. (A) Historical 4-color staining method: cluster resolution and phenotypic characteristics of mDC and pDC subsets. DC subsets were stained with lineage (lin) mAb cocktail (anti-CD3,−14,−19,−20) and with anti-CD11c and anti-CD123 (IL-3R α). mDC are lin- CD11c⁺ HLA-DR+ cells; pDC are lin-, CD123^bright HLA-DR+. (B) Direct DC subset-specific mAb staining method: cluster resolution and phenotypic characteristics of mDC1 and pDC subset precursors. PBMC were stained with lin mAbs, BDCA-1 and BDCA-2. BDCA-1⁺ lin⁻cells are considered mDC1. Lin- BDCA-2⁺ cells are pDC. (Reproduced from Tokita D. et al Transplantation 2008; 85:369)