Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice.
Susceptibility of activated T cells to apoptosis must be tightly regulated to ensure sufficient T cell progeny for an effective response, while allowing a rapid depletion of them at the end of the immune response. We show here that a previously isolated, NF-kappa B/rel target gene IEX-1 (Immediate Early response gene X-1) is highly expressed in T cells at early stages of activation, but declines with a prolonged period of activation time, coincident with an increased susceptibility of T cells to apoptosis during the late phases of an immune response. Transgenic expression of IEX-1 specifically in lymphocytes impaired apoptosis in activated T cells, extended a duration of an effector-phase of a specific immune response, and increased the accumulation of effector/memory-like T cells and the susceptibility to a lupus-like autoimmune disease. Our study demonstrated an antiapoptotic effect of IEX-1 on T cell apoptosis triggered by ligation of Fas and T cell receptor (TCR)/CD3 complex. The ability of extending life expectancy of T effectors, in line with a decrease in its expression following prolonged T cell activation, suggests a key role for IEX-1 in regulating T cell homeostasis during immune responses.
Zhang
Y
Y
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Schlossman
S F
SF
Edwards
R A
RA
Ou
Ching-Nan
CN
Gu
J
J
Wu
Mei X
MX
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016922:Cellular Senescence / Q000235:genetics; D006801:Humans; D006968:Hypersensitivity, Delayed; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008206:Lymphatic Diseases / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009363:Neoplasm Proteins; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019014:fas Receptor