Immune tolerance after delivery of dying cells to dendritic cells in situ.
Peripheral immune tolerance is believed to be induced by the processing and presentation of self-tissues that die during physiologic tissue turnover. To examine the mechanism that mediates tolerance, we injected mice with dying syngeneic TAP(-/-) splenocytes loaded with small amounts of the protein antigen, ovalbumin (OVA). After ingestion and presentation of cell-associated OVA by the CD8(+) subset of dendritic cells in situ, large numbers of antigen-reactive, CD8(+) T cell receptor (TCR) transgenic T lymphocytes were driven into cell cycle, but then the T cells were deleted. The animals were also tolerant to challenge with OVA in complete Freund's adjuvant. An agonistic anti-CD40 monoclonal antibody was then administered together with the OVA-loaded splenocytes, so that the dendritic cells in the recipient mice would mature. In contrast to observations made in the steady state, the antigen-reactive T cells expanded in numbers for 1-2 wk and produced large amounts of interleukin 2 and interferon gamma, while the animals retained responsiveness to antigen rechallenge. The specific tolerance that develops when dendritic cells process self tissues in the steady state should prevent or reduce the development of autoimmunity when dying cells are subsequently processed during infection.
Liu
Kang
K
Laboratory of Cellular Physiology and Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021, USA.
Iyoda
Tomonori
T
Saternus
Marzena
M
Kimura
Yukino
Y
Inaba
Kayo
K
Steinman
Ralph M
RM
D019264:Adoptive Transfer; D000818:Animals; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016923:Cell Death; D002455:Cell Division; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D019013:CD40 Antigens