A novel mutation in CD83 results in the development of a unique population of CD4+ T cells.
Using a mouse mutagenesis screen, we have identified CD83 as being critical for the development of CD4(+) T cells and for their function postactivation. CD11c(+) dendritic cells develop and function normally in mice with a mutated CD83 gene but CD4(+) T cell development is substantially reduced. Additionally, we now show that those CD4(+) cells that develop in a CD83 mutant animal fail to respond normally following allogeneic stimulation. This is at least in part due to an altered cytokine expression pattern characterized by an increased production of IL-4 and IL-10 and diminished IL-2 production. Thus, in addition to its role in selection of CD4(+) T cells, absence of CD83 results in the generation of cells with an altered activation and cytokine profile.
Celltech Research & Development, Bothell, WA 98021, USA.
Leon F
LF
García-Martínez
Mark W
MW
Appleby
Karen
K
Staehling-Hampton
Dawn M
DM
Andrews
Yuching
Y
Chen
Mark
M
McEuen
Phuong
P
Tang
Rebecca L
RL
Rhinehart
Sean
S
Proll
Bryan
B
Paeper
Mary E
ME
Brunkow
Andres G
AG
Grandea
Edward D
ED
Howard
Don E
DE
Walker
Patrick
P
Charmley
Mechthild
M
Jonas
Stevan
S
Shaw
John A
JA
Latham
Fred
F
Ramsdell
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007136:Immunoglobulins / Q000235:genetics* / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D000097802:CD83 Antigen
D015703:Antigens, CD; D016207:Cytokines; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen