CD4+ T lymphocytes with constitutive CD40 ligand in preautoimmune (NZB x NZW)F1 lupus-prone mice: phenotype and possible role in autoreactivity

J Immunol. 2000 Oct 1;165(7):4095-104. doi: 10.4049/jimmunol.165.7.4095.

Abstract

Lupus disease is marked by B lymphocyte hyperactivity and the production of Abs to dsDNA. The production of these anti-dsDNA Abs is T lymphocyte dependent. However, it is not clear how CD4+ T lymphocytes provide help for B lymphocytes to produce IgG anti-dsDNA Abs. One possible mechanism is suggested by studies showing that human patients with systemic lupus erythematosus and lupus mice have increased numbers of CD40 ligand (CD40L)+ T and B lymphocytes. The results described in this study reveal that young, clinically healthy lupus-prone New Zealand Black x New Zealand White F1 (BWF1) mice have naive CD4+ T cells with preformed CD40L. These cells contribute to a brisk response to immunization and to the production of anti-dsDNA Abs. In vitro experiments revealed that CD4+ T cells with preformed CD40L could, upon stimulation, provide antiapoptotic signals for B cells but could not induce proliferation or reduce activation threshold. These results suggest that the direct target cells for the effect of T cells with preformed CD40L in lupus may not be B lymphocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / immunology
  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Antibodies, Antinuclear / blood
  • Antigens / administration & dosage
  • Antigens / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • CD40 Ligand / biosynthesis
  • CD40 Ligand / immunology*
  • Cell Aggregation / immunology
  • Cell Differentiation / immunology
  • Cell Division / genetics
  • Cell Division / immunology
  • Cell Survival / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Crosses, Genetic
  • Cytoplasm / immunology
  • Cytoplasm / metabolism
  • DNA / immunology
  • Genetic Predisposition to Disease*
  • Immunization
  • Immunophenotyping
  • Kinetics
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Lymphocyte Activation
  • Lymphocyte Cooperation / immunology
  • Lymphocyte Count
  • Mice
  • Mice, Inbred CBA
  • Mice, Inbred NZB
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • Antibodies, Antinuclear
  • Antigens
  • CD40 Ligand
  • DNA