Biased T cell receptor V beta gene usage during specific stages of the development of autoimmune sialadenitis in the MRL/lpr mouse model of Sjögren's syndrome

Arthritis Rheum. 1995 Aug;38(8):1077-84. doi: 10.1002/art.1780380809.

Abstract

Objective: To analyze the repertoire of T cell receptor (TCR) V beta gene transcribed and expressed within the autoimmune lesions of the salivary gland in the MRL/lpr mouse model of Sjögren's syndrome.

Methods: Monoclonal antibodies (MAb) were used to determine the prevalence of selected V gene elements on T cell infiltrates from salivary glands of MRL/lpr mice. To analyze TCR V beta gene usage, we used reverse-transcriptase polymerase chain reaction (RT-PCR) and single-strand conformational polymorphism (SSCP) analyses.

Results: A predominance of V beta 8+ T cells was detected within the inflammatory lesions during development of autoimmune disease (confirmed by flow cytometry). RT-PCR analysis revealed that in autoimmune sialadenitis, the predominant expression of the V beta 8 gene segment began in the early stages of disease (2-month-old mice) and increased over time. Extensive age-related diversity of TCR V beta gene usage was also observed. SSCP analysis demonstrated a distinct and common binding pattern of the V beta 8 gene PCR product from the cell infiltrates during the course of the disease.

Conclusion: Our data suggest that in the MRL/lpr mouse model of Sjögren's syndrome, there is restricted usage of TCR V beta elements according to the stage of the disease, and that V beta 8 are probably used preferentially in the recognition of a single unknown self antigen in the salivary gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Autoimmune Diseases / genetics
  • Base Sequence
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Count
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gene Expression / immunology
  • Immunohistochemistry
  • Inflammation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains / genetics
  • Mice, Inbred Strains / immunology*
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Receptors, Antigen, T-Cell / genetics*
  • Salivary Glands / cytology
  • Salivary Glands / immunology
  • Sialadenitis / genetics*
  • Sialadenitis / immunology*
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / immunology
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Receptors, Antigen, T-Cell