Analysis of soluble and cell surface factors regulating anti-DNA topoisomerase I autoantibody production demonstrates synergy between Th1 and Th2 autoreactive T cells. Academic Article uri icon

Overview

abstract

  • The cellular and subcellular events governing Ab production with specificity for self Ags are poorly understood. In this study we examined the role of cellular interactions and cytokines in regulating the production of anti-DNA topoisomerase I (topo I) Ab, a major autoantibody in patients with systemic sclerosis (SSc). Topo I-specific T cell clones derived from SSc subjects and healthy donors were cultured with autologous peripheral blood B cells. Anti-topo I Ab production was induced by five of seven topo I-specific T cell clones derived from SSc subjects, but by none of eight T cell clones generated from healthy controls. However, two of the T cell clones from healthy controls provided help to HLA-DR-matched SSc B cells to produce anti-topo I Ab. The analysis of cytokine mRNA expression revealed that the ability to promote anti-topo I autoantibody production was strictly correlated with IL-2 and IL-6 expression by the T cell clones. Kinetic studies showed that IL-2 was required throughout the culture period for maximal autoantibody production and that both MHC-TCR and CD40-CD40L interactions were essential during the early phase of the culture. IL-6 was important in the late phase. Th1 clones (producing IL-2, but no IL-6) and Th2 clones (producing IL-6, but no IL-2) synergically activated autologous B cells to produce anti-topo I Ab. These results indicate that T cell-dependent B cell activation resulting in anti-topo I autoantibody production requires a series of temporally defined cell contact and soluble stimuli.

publication date

  • June 15, 2000

Research

keywords

  • Autoantibodies
  • Autoantigens
  • Cytokines
  • DNA Topoisomerases, Type I
  • Lymphocyte Cooperation
  • Membrane Proteins
  • Th1 Cells
  • Th2 Cells

Identity

Scopus Document Identifier

  • 0034659754

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.164.12.6138

PubMed ID

  • 10843663

Additional Document Info

volume

  • 164

issue

  • 12