Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice

Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):878-83. doi: 10.1073/pnas.022326699. Epub 2002 Jan 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis / immunology
  • Apoptosis Regulatory Proteins
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Cellular Senescence / genetics
  • Humans
  • Hypersensitivity, Delayed
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / physiology
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / pathology
  • Lymphatic Diseases / genetics
  • Lymphatic Diseases / immunology
  • Lymphocyte Activation / genetics*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Neoplasm Proteins*
  • Splenomegaly / genetics
  • Splenomegaly / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • fas Receptor / metabolism


  • Apoptosis Regulatory Proteins
  • IER3 protein, human
  • Immediate-Early Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Neoplasm Proteins
  • fas Receptor