Restoration of an early, progressive defect in responsiveness to T-cell activation in lupus mice by exogenous IL-2

Autoimmunity. 1993;15(1):19-29. doi: 10.3109/08916939309004835.

Abstract

Splenic T-cells from lupus strain (NZB/W F1, Mrl/lpr) mice lack the ability to respond to concanavalin A (Con A) by secretion of IL-2 and hence expression of IL-2 receptor and proliferation. These defects were found not only in an aged group (> 5 months) of mice in which obvious clinical 'SLE like' symptoms and elevated levels of serum autoantibodies were observed, but also in mice as young as 4-wk. We demonstrate here that the defective mitogenic activation of T-cells from lupus mice is due to the inability of T-helper cells to produce IL-2 and this defect can be restored by exogenous IL-2 in vitro. Con A-induced cell proliferation and IL-2 receptor expression on CD3+ cells from lupus mice occur only in the presence of exogenous IL-2, whereas normal T-cells from BALB/c and CBA control mice are activated by the mitogen and undergo complete cell cycling in the absence of exogenous IL-2, as they are able to secrete sufficient endogenous IL-2. The detection of impaired T-helper function in young lupus mice, before development of overt disease, and the reversible nature of the defect indicate that defective IL-2 activity may be fundamental to the mechanism of development of pathology in SLE.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Female
  • Interleukin-2 / deficiency
  • Interleukin-2 / metabolism
  • Interleukin-2 / pharmacology*
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation / drug effects*
  • Mice
  • Mice, Inbred BALB C / immunology
  • Mice, Inbred CBA / immunology
  • Mice, Inbred NZB / immunology*
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • Interleukin-2
  • Receptors, Interleukin-2
  • Concanavalin A