Most lymphoid organ dendritic cell types are phenotypically and functionally immature.
Dendritic cells (DCs) have been thought to follow a life history, typified by Langerhans cells (LCs), with 2 major developmental stages: an immature stage that captures antigens in the periphery and a mature stage that presents those antigens in the lymphoid organs. However, a systematic assessment of the maturity of lymphoid organ DCs has been lacking. We have analyzed the maturity of the DC types found in the steady state in the spleen, lymph nodes (LNs), and thymus. The DCs that migrate into the iliac, mesenteric, mediastinal, or subcutaneous LNs from peripheral tissues were mature and therefore could not process and present newly encountered antigens. However, all the other DC types were phenotypically and functionally immature: they expressed low levels of surface major histocompatibility complex class II (MHC II) and CD86, accumulated MHC II in their endosomes, and could present newly encountered antigens. These immature DCs could be induced to mature by culture in vitro or by inoculation of inflammatory stimuli in vivo. Therefore, the lymphoid organs contain a large cohort of immature DCs, most likely for the maintenance of peripheral tolerance, which can respond to infections reaching those organs and mature in situ.
Wilson
Nicholas S
NS
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3050, Australia.
El-Sukkari
Dima
D
Belz
Gabrielle T
GT
Smith
Christopher M
CM
Steptoe
Raymond J
RJ
Heath
William R
WR
Shortman
Ken
K
Villadangos
José A
JA
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007108:Immune Tolerance / Q000276:immunology*; D016130:Immunophenotyping; D066298:In Vitro Techniques; D008198:Lymph Nodes / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016707:Tissue Fixation
D000949:Histocompatibility Antigens Class II