Ex-Vivo treatment of antigen presenting cells with CTLA4Ig and peptide prevents EAE in the lewis rat

R. Verburg, A. Chandraker, L. Gallon, W. W. Hancock, M. H. Savejrh, S. J. Khoury

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1 Scopus citations

Abstract

We have shown that systemic administration of CTLA4Ig is effective in preventing experimental autoimmune encephalomyelitis (EAE) in Lewis rats (J Iminimol 1995; 155:4521). In this study we investigated the mechanisms of CD28-B7 blockade in EAE. Naive APCs (nylon wool adherent splenocytes) incubated in vitro with CTLA4Ig and the encephalitogenic peptide of MBP (p71-90) protect recipients from EAE: Lewis rats were immunized with MBP/CFA 48 hours after receiving 40x10APCs i.v. Animals received APCs incubated with CTLA4Ig+p71-90, control animals received APCs incubated with CTLA4Ig with no peptide, or no APCs. Grade Incidence Mean Duration Index Control (n=15) 2.60 ± 0.18 100% 4.40 ± 0.25 11.44 APC + peptide + CTLA4-Ig (n=12) 0.75 ± 0.21 58% 1.75 ± 0.46 0.77 APC + CTLA4-Ig control (n=7) 2.29 ± 0.52 100% 4.57 ± 0.30 10.47 In vitro, lymphocytes from protected animals had decreased proliferation to MBP, as compared to controls. We then investigated which APC is mediating protection. The dendritic-enriched population of splenocytes, but not T or B cell-enriched preparations, was able to induce tolerance when pre-incubated with CTLA4Ig and p71-90. Incubating dendritic-enriched cells with p71-90 alone was not protective. Immunohistologically, protected animals had decreased inflammatory response with inhibition of Thl cytokines and sparing of Th2 cytokines in the brain. These results suggest that ex-vivo blockade of CD28-B7 leads to the generation of regulatory cells, presumably Th2, which inhibit priming of T cells and suppress the autoimmune response to the specific antigen in vivo.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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