Impaired T cell death and lupus-like autoimmunity in T cell-specific adapter protein-deficient mice

Jorn Drappa, Lynn A. Kamen, Elena Chan, Maria Georgiev, Dalit Ashany, Francesc Marti, Philip D. King

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


T cell-specific adaptor protein (TSAd) is a T lineage-restricted signaling adaptor molecule that is thought to participate in the assembly of intracellular signaling complexes in T cells. Previous studies of TSAd-deficient mice have revealed a role for TSAd in the induction of T cell interleukin 2 secretion and proliferation. We now show that TSAd-deficient mice are susceptible to lupus-like autoimmune disease. On the nonautoimmune-prone C57BL/6 genetic background, TSAd deficiency results in hypergammaglobulinemia that affects all immunoglobulin (Ig)G subclasses. Older C57BL/6 TSAd-deficient mice (1 yr of age) accumulate large numbers of activated T and B cells in spleen, produce autoantibodies against a variety of self-targets including single stranded (ss) and double stranded (ds) DNA, and, in addition, develop glomerulonephritis. We further show that immunization of younger C57BL/6 TSAd-deficient mice (at age 2 mo) with pristane, a recognized nonspecific inflammatory trigger of lupus, results in more severe glomerulonephritis compared with C57BL/6 controls and the production of high titer ss and ds DNA antibodies of the IgG subclass that are not normally produced by C57BL/6 mice in this model. The development of autoimmunity in TSAd-deficient mice is associated with defective T cell death in vivo. These findings illustrate the role of TSAd as a critical regulator of T cell death whose absence promotes systemic autoimmunity.

Original languageEnglish
Pages (from-to)809-821
Number of pages13
JournalJournal of Experimental Medicine
Issue number5
StatePublished - Sep 1 2003


  • Apoptosis
  • Autoimmunity
  • Glomerulonephritis
  • Signal transduction
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Impaired T cell death and lupus-like autoimmunity in T cell-specific adapter protein-deficient mice'. Together they form a unique fingerprint.

Cite this