T cells signaled by NF-kappa B- dendritic cells are sensitized not anergic to subsequent activation


Autoria(s): Thompson, Angus G.; O'Sullivan, Brendan J.; Beamish, Heather; Thomas, Ranjeny
Contribuinte(s)

Boss, J. M.

Hogan, M. M.

Data(s)

01/01/2004

Resumo

Paradoxically, while peripheral self-tolerance exists for constitutively presented somatic self Ag, self-peptide recognized in the context of MHC class II has been shown to sensitize T cells for subsequent activation. We have shown that MHC class II(+)CD86(+)CD40(-) DC, which can be generated from bone marrow in the presence of an NF-kappaB inhibitor, and which constitutively populate peripheral tissues and lymphoid organs in naive animals, can induce Ag-specific tolerance. In this study, we show that CD40(-) human monocyte-derived dendritic cells (DC), generated in the presence of an NF-kappaB inhibitor, signal phosphorylation of TCRzeta, but little proliferation or IFN-gamma in vitro. Proliferation is arrested in the G(1)/G(0) phase of the cell cycle. Surprisingly, responding T cells are neither anergic nor regulatory, but are sensitized for subsequent IFN-gamma production. The data indicate that signaling through NF-kappaB determines the capacity of DC to stimulate T cell proliferation. Functionally, NF-kappaB(-)CD40(-)class II+ DC may either tolerize or sensitize T cells. Thus, while CD40(-) DC appear to prime or prepare T cells, the data imply that signals derived from other cells drive the generation either of Ag-specific regulatory or effector cells in vivo.

Identificador

http://espace.library.uq.edu.au/view/UQ:72322

Idioma(s)

eng

Publicador

American Association of Immunologists

Palavras-Chave #Immunology #Cd40 Ligand Expression #In-vivo #Rheumatoid-arthritis #Antigen Presentation #Cytokine Production #Self-recognition #Apoptotic Cells #Foreign Antigen #Induction #Relb #C1 #320207 Autoimmunity #730102 Immune system and allergy #110322 Rheumatology and Arthritis #1107 Immunology
Tipo

Journal Article