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Dendritic Cell Function in Vivo during the Steady State: A Role in Peripheral Tolerance
Author(s) -
STEINMAN RALPH M.,
HAWIGER DANIEL,
LIU KANG,
BONIFAZ LAURA,
BONNYAY DAVID,
MAHNKE KARSTEN,
IYODA TOMONORI,
RAVETCH JEFFREY,
DHODAPKAR MADHAV,
INABA KAYO,
NUSSENZWEIG MICHEL
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb06029.x
Subject(s) - antigen , immunology , immune system , dendritic cell , antigen presenting cell , biology , microbiology and biotechnology , inflammation , antigen presentation , immune tolerance , autoimmunity , peripheral tolerance , t cell
A bstract : The avoidance of autoimmunity requires mechanisms to actively silence or tolerize self reactive T cells in the periphery. During infection, dendritic cells are not only capturing microbial antigens, but also are processing self antigens from dying cells as well as innocuous environmental proteins. Since the dendritic cells are maturing in response to microbial and other stimuli, peptides will be presented from both noxious and innocuous antigens. Therefore it would be valuable to have mechanisms whereby dendritic cells, prior to infection, establish tolerance to those self and environmental antigens that can be processed upon pathogen encounter. In the steady state, prior to acute infection and inflammation, dendritic cells are in an immature state and not fully differentiated to carry out their known roles as inducers of immunity. These immature cells are not inactive, however. They continuously circulate through tissues and into lymphoid organs, capturing self antigens as well as innocuous environmental proteins. Recent experiments have provided direct evidence that antigen‐loaded immature dendritic in vivo silence T cells either by deleting them or by expanding regulatory T cells. In this way, it is proposed that the immune system overcomes at least some of the risk of developing autoimmunity and chronic inflammation. It is proposed that dendritic cells play a major role in defining immunologic self, not only centrally in the thymus but also in the periphery.