Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta.
In mice lacking the interleukin-2 receptor beta chain (IL-2R beta), T cells were shown to be spontaneously activated, resulting in exhaustive differentiation of B cells into plasma cells and the appearance of high serum concentrations of immunoglobulins G1 and E as well as autoantibodies that cause hemolytic anemia. Marked infiltrative granulocytopoiesis was also apparent, and the animals died after about 12 weeks. Depletion of CD4+ T cells in mutant mice rescued B cells without reversion of granulocyte abnormalities. T cells did not proliferate in response to polyclonal activators, nor could antigen-specific immune responses be elicited. Thus, IL-2R beta is required to keep the activation programs of T cells under control, to maintain homeostasis, and to prevent autoimmunity.
Suzuki
H
H
Amgen Institute, Toronto, Ontario, Canada.
Kündig
T M
TM
Furlonger
C
C
Wakeham
A
A
Timms
E
E
Matsuyama
T
T
Schmits
R
R
Simard
J J
JJ
Ohashi
P S
PS
Griesser
H
H
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016254:Mutagenesis, Insertional; D009196:Myeloproliferative Disorders / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D001323:Autoantibodies; D015375:Receptors, Interleukin-2