myelin-basic-protein and Trypanosomiasis--African

CD-1 mice infected with the protozoan parasite Trypanosoma brucei brucei developed few signs of central nervous system pathology associated with the invasion of the central nervous system by these parasites and did not survive beyond 5-6 weeks with deaths common before this time point. However, use of the trypanocidal drug diminazene aceturate (40 mg/kg), which fails to cross the blood-brain barrier, on day 21 post-infection led to the development of central nervous system pathology similar to that seen in the fatal post-treatment reactive encephalopathies that can occur in human African trypanosomiasis. Enzyme-linked immunosorbent assays were used to measure autoantibody titres to double-stranded DNA, myelin basic protein and to the myelin-specific galactocerebrosides and gangliosides in groups of infected mice, with or without the post-treatment reaction, on day 30 post-infection and compared with uninfected controls. Infection with T. brucei brucei raised the titres of all of these autoantibodies. Treatment of infected mice with diminazene aceturate resulted in elevated levels of all of these autoantibodies compared to the untreated animals. There was a strong positive correlation between the central nervous system pathology and the levels of autoantibodies to myelin basic protein, galactocerebrosides and gangliosides, but not to double-stranded DNA. The elevated titres observed may be a consequence of the polyclonal B cell activation that is believed to occur in African trypanosomiasis, parasite epitopes that are cross-reactive with these central nervous system (CNS)-specific antigens or result from the CNS damage associated with sub-curative chemotherapy.

Topics: Animals; Antibodies, Antinuclear; Autoantibodies; Brain; Female; Galactosylceramides; Gangliosides; Mice; Myelin Basic Protein; Trypanosomiasis, African

PVG/c rats, infected 3 days previously with 10(3) Trypanosoma brucei brucei S.42 organisms failed to develop adjuvant disease in response to an intradermal inoculation of mycobacterial adjuvant. By contrast, similarly infected rats, immunized with heterologous brain and spinal cord in Freund's complete adjuvant with pertussis vaccine as a secondary adjuvant, developed clinical signs of allergic encephalomyelitis (EAE) at least as severe as those in uninfected rats. Delayed hypersensitivity reactions to PPD were depressed in trypanosome-infected, adjuvant-injected rats, as were the reactions to myelin basic protein in infected rats developing EAE. There appeared to be no cross-reactivity between trypanosomal antigen and myelin basic protein which could account for the lack of suppression of EAE. It is suggested that the different extent to which autoimmunity is involved in these two experimental allergic diseases may account for the differential suppressive activity of trypanosome infections upon them.

Topics: Animals; Arthritis, Experimental; Cross Reactions; Encephalomyelitis, Autoimmune, Experimental; Female; Hypersensitivity, Delayed; Immunosuppression Therapy; Male; Myelin Basic Protein; Rats; Skin Tests; Time Factors; Trypanosoma brucei brucei; Trypanosomiasis, African; Tuberculin