THYMUS CHANGES IN EXPERIMENTALLY-INDUCED MYASTHENIA-GRAVIS

Experimental myasthenia gravis (EMG) was elicited in female AO rats, 8-12 weeks of age, by injection of 100 mug/rat Torpedo marmorata acetylcholine receptor (AChR)-protein incorporated in CFA. Bordetella pertussis, 24 x 10(9) microorganisms, rat, was injected simultaneously as additional adjuvant. Rats were sacrificed on the day of appearance of the clinical signs of EMG, and thymuses were used for histological analysis using stereologic method, and thymocyte subsets were estimated by flow cytometry. Two and three colour fluorescence was applied to determine DN (CD4- CD8-), DP (CD4+CD8+), SP-CD4+ (CD4+CD8-) and SP-CD8+ (CD4-CD8+) subsets, as well as thymocytes expressing TCR alpha/beta. Rats immunized with BSA and rats injected with saline were used as controls. From 56 rats immunized with AChR-protein, 44 rats developed the disease, between day 7 and 11 after immunization. Severity of disease varied from + to + + +. Stereologic analysis of tissue sections revealed a highly significant reduction of thymic cortex and hypertrophy of medulla in EMG thymuses. Similar, but very slight changes were observed in thymuses of rats immunized with BSA. Percentages of DN, SP-CD4+, and SP-CD8+ subpopulations were significantly increased, while the percentage of DP population showed a marked decrease. These preliminary data suggest an alteration of thymocyte maturational events. Whether these changes could be responsible for the initiation of autoimmunity, or are occurring as a secondary phenomenon, after EMG was already established following the injection of cross reactive antigen, is a matter for discussion.