Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus

J Exp Med. 1991 Jan 1;173(1):127-36. doi: 10.1084/jem.173.1.127.

Abstract

Transplantation of bone marrow cells of lpr/lpr mice into irradiated normal mice fails to develop massive lymphadenopathy or autoimmunity but causes severe graft-vs.-host-like syndrome. To elucidate an abnormality of lpr/lpr bone marrow-derived T cells, we transplanted bone marrow cells of Mlsb lpr/lpr mice into H-2-compatible Mlsa non-lpr mice. Although lpr/lpr T cell precursors repopulated the host thymus as well as +/+ cells, a proportion of CD4+CD8+ cells decreased, and that of both CD4- and CD8- single-positive cells increased compared with those of +/+ recipients. Notably, in MRL/lpr----AKR and C3H/lpr----AKR chimeras, CD4 single-positive thymocytes contained an increased number of V beta 6+ cells in spite of potentially deleting alleles of Mlsa, whereas V beta 6+ mature T cells were deleted in the MRL/+ ----AKR and C3H/+ ----AKR chimeras. There was no difference between MRL/+ ----AKR and MRL/lpr----AKR chimeras in their proportion of V beta 3+ cells because both host and donor strain lack the deleting alleles. Interleukin 2 receptor expression of mature T cells, in the thymus and lymph node, was obviously higher in the MRL/lpr----AKR chimeras, in particular in the "forbidden" V beta 6+ subset. Moreover, lpr donor-derived peripheral T cells showed vigorous anti-CD3 response. These results indicate that lpr-derived T cells escape not only tolerance-related clonal deletion but also some induction of unresponsiveness in the non-lpr thymus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Bone Marrow Transplantation / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Lymphocyte Activation
  • Lymphoproliferative Disorders / genetics*
  • Lymphoproliferative Disorders / immunology
  • Mice
  • Mice, Inbred Strains
  • Radiation Chimera
  • Receptors, Antigen, T-Cell / analysis
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*

Substances

  • Receptors, Antigen, T-Cell