Where, when, and how to detect biased expression of disease-relevant Vβ genes in rats with experimental autoimmune encephalomyelitis

H. Offner, A. C. Buenafe, M. Vainiene, B. Celnik, A. D. Weinberg, D. P. Gold, G. Hashim, A. A. Vandenbark

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

The biased use of Vβ8.2 and Vβ6 in rats by encephalitogenic T cells specific for the S72-89 and S87-99 epitopes of guinea pig basic protein (Gp- BP) has allowed the use of anti-Vβ antibodies and synthetic TCR peptides for treatment of experimental autoimmune encephalomyelitis (EAE). Striking V gene biases also occur in human autoimmune diseases, raising the question of to what degree these biases reflect potentially pathogenic T cells. To address this question, we evaluated the expression of the EAE-associated marker Vβ8.2 and Vβ6 molecules in the periphery, spinal cord (SC), and cerebrospinal fluid (CSF) during the course of EAE, in unselected, IL-2- expanded, and Gp-BP-restimulated populations. In CSF cells, there was a strong bias for the marker Vβ before the onset of EAE, but this bias was not enhanced by IL-2, which skewed the CSF population to >80% CD8+ T cells. In SC, the marker Vβ were expressed optimally during the onset of EAE, even in unselected cells, and this bias could be enhanced sequentially by IL-2 expansion and Gp-BP restimulation. During the recovery phase, however, the marker Vβ8.2 bias was obfuscated by the appearance of a heterogeneous Vβ T cell population. Biased expression of the marker V genes was not detected in unselected or IL-2-expanded peripheral cells at any time during EAE. These data suggest that peripheral T cells bearing the disease-relevant V genes first appeared in CSF before disease onset and then migrated to SC beginning on the first day of clinical signs. During the recovery phase of the disease, these cells were diluted by an influx of T cells bearing other Vβ genes, requiring restimulation with Gp-BP to observe the Vβ8.2 bias. These data have important implications for the interpretation of Vβ gene biases that have been reported in human autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)506-517
Number of pages12
JournalJournal of Immunology
Volume151
Issue number1
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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