Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes.
Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8(+) T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the alphavbeta5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the alphavbeta5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the alphavbeta5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York 10021, USA.
M L
ML
Albert
S F
SF
Pearce
L M
LM
Francisco
B
B
Sauter
P
P
Roy
R L
RL
Silverstein
N
N
Bhardwaj
D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD; D017209:Apoptosis; D018955:CD36 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D010587:Phagocytosis; D019030:Receptors, Vitronectin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018955:CD36 Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D016023:Integrins; D008562:Membrane Glycoproteins; D019030:Receptors, Vitronectin; D000097802:CD83 Antigen; C064660:integrin alphaVbeta5