Transfer of experimental allergic neuritis by intra neural injection of sensitized lymphocytes.
The final mediators of immune injury in EAN were investigated by intraneural injection of sensitized lymphocytes. Unfractionated specifically sensitized cells caused conduction block which was evident within 24 h after injection, reached significance within 3 days and remained depressed for over 12 days. Pathological changes at the site of injection showed infiltrating lymphoid and mononuclear cells and significant demyelination. The latter was only evident several days after the electrophysiological changes. These effects were shown to be specific, as injection of LNC from normal rats or those immunized with CFA alone did not induce the changes. Fractionation of sensitized LNC into the CD4+ and CD8+ subsets of T-cells showed only the former caused a drop in the amplitude ratio of nerve conduction. These changes in conduction were comparable to those observed in rats immunized with myelin/CFA to induce active EAN. Cyclosporin A (CSA) was given to host animals to block production of cytokines by the injected cells. This inhibited macrophage accumulation at the site of injection, but did not stop the electrophysiological changes. This result suggested that there was direct T-cell damage rather than damage consequent upon macrophage activation. These studies developed a model in which the cellular and molecular mechanisms of conduction block and demyelination in EAN can be studied by direct injection of specifically sensitized LNC.
Hodgkinson
S J
SJ
Department of Neurology, University of Sydney, N.S.W., Australia.
Westland
K W
KW
Pollard
J D
JD
D000818:Animals; D000911:Antibodies, Monoclonal; D002417:Cattle; D004594:Electrophysiology / Q000379:methods; D005260:Female; D005620:Freund's Adjuvant; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007114:Immunization; D007124:Immunoenzyme Techniques; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D017710:Lymphocyte Transfusion; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D009186:Myelin Sheath; D009431:Neural Conduction; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D005620:Freund's Adjuvant