Decreased CD4-CD8- TCR-alpha beta + cells in lpr/lpr mice lacking beta 2-microglobulin

J Immunol. 1995 Mar 1;154(5):2063-74.


The CD4-CD8- T cells that accumulate in lpr/lpr mice have previously expressed CD8, on the basis of studies of CD8 alpha gene demethylation. The actual requirement for CD8 interaction with class I MHC molecules to promote the appearance of CD4-CD8- T cells in lpr/lpr mice has also been suggested. To examine this point in more detail, the lpr mutation was bred onto a beta 2-microglobulin-deficient background (beta 2-m-/-). C57BL/6 (B6) mice homozygous for both the lpr mutation of the fas gene and inactivation of the beta 2-m gene (beta 2-m-/- lpr/lpr) develop less alpha beta T cell lymphadenopathy than the parental B6 lpr/lpr strain. This is caused by the near absence of CD8+ T cells and a considerable reduction in CD4-CD8- T cells, revealing an important role for positive selection on class I MHC molecules during the ontogeny of lpr CD4-CD8- T cells. Although absolute numbers of peripheral T cells are decreased in beta 2-m-/- lpr/lpr mice, they manifest a B cell lymphadenopathy with age. beta 2-m-/- lpr/lpr mice display only subtle indications of autoimmune disease with age, compared with parental B6 (beta 2-m+/+)lpr/lpr mice. These include limited histopathologic stages of kidney disease and lack of proteinuria, despite the presence of serum anti-DNA Abs. Thus, absence of class I MHC-positive selection of CD8+ and CD4-CD8- TCR-alpha beta + cells limits the autoimmune diathesis observed in beta 2-m+/+ lpr/lpr mice.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Base Sequence
  • CD4 Antigens / metabolism*
  • CD8 Antigens / metabolism*
  • DNA Primers / genetics
  • DNA Transposable Elements
  • Kidney Diseases / genetics
  • Kidney Diseases / immunology
  • Kidney Diseases / pathology
  • Lymphatic Diseases / genetics
  • Lymphatic Diseases / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Oncogenes
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • beta 2-Microglobulin / deficiency*
  • beta 2-Microglobulin / genetics


  • Antibodies, Antinuclear
  • CD4 Antigens
  • CD8 Antigens
  • DNA Primers
  • DNA Transposable Elements
  • Receptors, Antigen, T-Cell, alpha-beta
  • beta 2-Microglobulin