WESTPORT, CT (Reuters Health) Oct 23 - Oral administration of myelin basic protein (MBP) causes early T-cell activation and T-cell receptor (TCR) downregulation in transgenic mice, and thereby protects against experimental allergic encephalomyelitis (EAE, an animal model of multiple sclerosis), according to a report in the October issue of the Journal of Clinical Investigation.
Antigen-specific cells are uncommon in wild-type mice, so Dr. Jacqueline M. Benson, from The Ohio State University in Columbus, Ohio, and colleagues studied the response to a high dose of orally administered MBP in transgenic mice that express a TCR specific for an encephalitogenic epitope of MBP.
MBP in repeated low doses diminished the MBP-specific T cells, the authors report, whereas single oral administration of high-dose MBP profoundly reduced the blood and lymph node numbers of MBP-specific T cells. The numbers returned to near normal by day 3 after feeding.
Fluorescent-labeled TCR was profoundly reduced after MBP feeding, but internal label was increased, the researchers note, suggesting that high-dose oral administration of MBP results in internalization of TCR.
During the time when surface TCR was reduced, transgenic mice were protected from EAE challenge, the report indicates, but by day 3 after feeding (when TCR expression was restored) they were no longer protected.
After day 3, MBP-specific T cells underwent a gradual decline in numbers, the investigators determined. Further experiments demonstrated late apoptosis of these T cells after high-dose oral MBP administration.
The researchers "have been pioneers both in the study of oral tolerance in the EAE model and in establishing the high-dose mechanism of anergy," comments Dr. Howard L. Weiner, from Harvard Medical School in Boston, elsewhere in the journal. "Their continued work further defines basic mechanisms associated with orally administered antigen, which should hasten the development of mucosally administered antigens for the treatment of human diseases."
J Clin Invest 2000;106:935-937,1031-1038.