Hydrogen peroxide as an immunological transmitter regulating autoreactive T cells.
CONCLUSIONS
An unexpected finding, revealed by positional cloning of genetic polymorphisms controlling models for rheumatoid arthritis, exposed a new function of Ncf1 and NADPH oxidase (NOX) 2 controlled oxidative burst.


BACKGROUND
A decreased capacity to produce ROS due to a natural polymorphism was found to be the major factor leading to more severe arthritis and increased T cell-dependent autoimmunity.


RESULTS
In the vein of this finding, we here review a possible new role of ROS in regulating inflammatory cell and autoreactive T cell activity. It is postulated that peroxide is an immunologic transmitter secreted by antigen-presenting cells that downregulate the responses by autoreactive T cells.


CONCLUSIONS
This may operate at different levels of T cell selection and activation: during negative selection in the thymus, priming of T cells in draining lymph nodes, and while interacting with macrophages in peripheral target tissues.
Medical Inflammation Research, MBB, Karolinska Institutet, Stockholm, Sweden. Rikard.Holmdahl@ki.se
Rikard
R
Holmdahl
Outi
O
Sareila
Angela
A
Pizzolla
Susann
S
Winter
Cecilia
C
Hagert
Noora
N
Jaakkola
Tiina
T
Kelkka
Lina M
LM
Olsson
Kajsa
K
Wing
Liselotte
L
Bäckdahl
D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007155:Immunologic Factors / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases