Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 1998 Oct 05;188(7):1359-68
Date
10/09/1998Pubmed ID
9763615Pubmed Central ID
PMC2212488DOI
10.1084/jem.188.7.1359Scopus ID
2-s2.0-3543053363 (requires institutional sign-in at Scopus site) 1091 CitationsAbstract
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.
Author List
Albert ML, Pearce SF, Francisco LM, Sauter B, Roy P, Silverstein RL, Bhardwaj NAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antigen PresentationAntigens, CD
Apoptosis
CD36 Antigens
Cells, Cultured
Dendritic Cells
Histocompatibility Antigens Class I
Humans
Immunoglobulins
Integrins
Macrophages
Membrane Glycoproteins
Phagocytosis
Receptors, Vitronectin
T-Lymphocytes, Cytotoxic
