The role of the thymus in development of necrotizing arteritis in transgenic rats carrying the env-pX gene of human T-cell leukemia virus type-I

Am J Pathol. 2002 Sep;161(3):755-61. doi: 10.1016/S0002-9440(10)64234-4.

Abstract

Necrotizing arteritis mimicking polyarteritis nodosa occurred in transgenic rats carrying the env-pX gene of human T-cell leukemia virus type I. To investigate the pathogenesis of necrotizing arteritis in these rats (env-pX rats), adoptive transfers of spleen cells and bone marrow cells were done from env-pX rats before they developed arteritis to nontransgenic rats. Necrotizing arteritis occurred in lethally irradiated nontransgenic rats reconstituted by env-pX spleen cells, thus indicating that the env-pX transgene in affected vessels may not be essential for the development of arteritis. In contrast, arteritis was not induced in nontransgenic recipients by adoptive transfers of env-pX bone marrow cells, which suggested that T cells derived from the env-pX thymus may play a role in the development of arteritis. To clarify if the process of differentiation of T cells in the env-pX thymus is crucial to develop necrotizing arteritis, reciprocal exchange of thymus frameworks was done between env-pX and nontransgenic rats. Necrotizing arteritis occurred in nontransgenic rats with an env-pX thymus framework, whereas development of arteritis was suppressed in env-pX rats in which the thymus framework was replaced with a nontransgenic one. This collective evidence shows that the thymus is directly associated with the development of necrotizing arteritis in env-pX rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Humans
  • Polyarteritis Nodosa / etiology
  • Polyarteritis Nodosa / genetics*
  • Polyarteritis Nodosa / immunology*
  • Rats
  • Retroviridae Proteins, Oncogenic / genetics*
  • T-Lymphocytes / immunology
  • Thymus Gland / immunology*
  • Transcription Factors*
  • Viral Envelope Proteins / genetics
  • Viral Regulatory and Accessory Proteins

Substances

  • Retroviridae Proteins, Oncogenic
  • Transcription Factors
  • Viral Envelope Proteins
  • Viral Regulatory and Accessory Proteins
  • pX protein, Human T-lymphotropic virus 1