B cells require "nurturing" by CD4 T cells during development in order to respond in chronic graft-versus-host model of systemic lupus erythematosus

Clin Immunol. 2010 Jul;136(1):105-15. doi: 10.1016/j.clim.2010.03.003. Epub 2010 Apr 8.

Abstract

The murine chronic GVH (cGVH) model of SLE is induced by allo-recognition of foreign major histocompatibility complex (MHC) class II determinants. Previous studies have shown that syngeneic CD4(+) T cells are needed during B cell development in order to induce cGVH response in CD4KO mice. Our present studies show that B cells require "nurturing" by CD4 T cells through much of their ontogeny in order to respond to allo-signaling and become autoreactive. The nurturing process does not require antigen-specific cognate interactions between CD4 T cells and B cells. It is mediated by IL-4, but not IL-10, IL-6 and IFN-gamma. The CD4 T cell nurturing may be supplanted by large doses of IL-4 and/or by agonistic anti-CD40 mAb. Understanding the mechanism of this "nurturing" process may yield clues to the role of CD4 T cells in lupus and in host defense in general.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Autoantibodies / blood
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD4 Antigens / genetics
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / transplantation
  • CD40 Antigens / agonists
  • CD40 Antigens / immunology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology*
  • Cytokines / genetics
  • Disease Models, Animal
  • Female
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / urine
  • Histocompatibility Antigens Class II / genetics
  • Homeodomain Proteins / genetics
  • Interleukin-4 / genetics
  • Interleukin-4 / pharmacology
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Lupus Erythematosus, Systemic / urine
  • Lymphocyte Activation / immunology
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Proteinuria / diagnosis
  • Receptors, Antigen, T-Cell / genetics
  • Skin / pathology

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Autoantibodies
  • CD4 Antigens
  • CD40 Antigens
  • Cytokines
  • Histocompatibility Antigens Class II
  • Homeodomain Proteins
  • Receptors, Antigen, T-Cell
  • RAG-1 protein
  • Interleukin-4