Impaired T cell death and lupus-like autoimmunity in T cell-specific adapter protein-deficient mice. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • September 1, 2003

Research

keywords

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Hypergammaglobulinemia
  • Lupus Erythematosus, Systemic
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC2194195

Scopus Document Identifier

  • 0042886906

Digital Object Identifier (DOI)

  • 10.1084/jem.20021358

PubMed ID

  • 12953096

Additional Document Info

volume

  • 198

issue

  • 5