Target organ-specific up-regulation of the MRC OX-40 marker and selective production of Th1 lymphokine mRNA by encephalitogenic T helper cells isolated from the spinal cord of rats with experimental autoimmune encephalomyelitis

A. D. Weinberg, J. J. Wallin, R. E. Jones, T. J. Sullivan, D. N. Bourdette, A. A. Vandenbark, H. Offner

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Lewis x Buffalo F. rat lymphocytes express both forms of the allelic marker RT7.1 (Lewis) and RT7.2 (Buffalo). We generated myelin basic protein (MBP)-specific encephalitogenic F1 T helper cell lines and adoptively transferred them into naive irradiated Lewis recipients, which enabled us to detect and isolate donor T cells (with RT7.2) within the recipients. The spinal cord and cerebrospinal fluid (CSF) were highly enriched for the donor T cells compared with the blood and spleen. The donor cell number peaked on the first day of disease in the spinal cord and CSF and decreased as the disease progressed. A high percentage of the donor T cells isolated from the spinal cord were positive for the T helper cell activation marker OX-40, whereas a (lower) percentage of CSF donor cells expressed OX-40. Donor cells isolated from blood or spleen were negative for OX-40 expression. In contrast, the IL-2 receptor (CD25) was positive on all the transferred T cells in all tissue sites examined. Cell sorting experiments showed that the MBP-specific donor cells were enriched for IFN-γ, IL-2, TNF-α, and IL-3 mRNA when compared with the host-recruited spinal cord cells, whereas similar amounts of IL-10 mRNA were produced by both populations. Lymphokine mRNA production was also enriched in donor T cells isolated from the spinal cord compared with donor T cells isolated from the spleen. The spinal cord donor cells produced higher levels of IL-2, IFN-γ, and IL-3 mRNA, whereas similar amounts of IL-10 and TNF-α mRNA were produced from donor cells isolated from the spleen and the spinal cord. Our data suggest that the amount/percentage, activation state, and enhanced lymphokine production at the site of inflammation are all important factors in determining the autoimmune potential of Ag-specific effector T helper cells.

Original languageEnglish (US)
Pages (from-to)4712-4721
Number of pages10
JournalJournal of Immunology
Volume152
Issue number9
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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