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Suppression of murine experimental autoimmune hepatitis by T‐cell vaccination or immunosuppression
Author(s) -
Lohse Ansgar W.,
Dienes HansPeter,
zum Büschenfelde KarlHermann Meyer
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510270611
Subject(s) - immunology , vaccination , immunosuppression , medicine , autoimmune hepatitis , t cell , immune system , adjuvant , azathioprine , splenocyte , autoimmune disease , hepatitis , immunotherapy , disease , antibody
Patients with autoimmune hepatitis (AIH) usually require immunosuppressive therapy for many years, if not for a lifetime. Experimental immunotherapy such as T‐cell vaccination aims at manipulating the immune system in such a way that autoimmunity is specifically regulated to enable long‐lasting correction of the disease process. We aimed to test the feasibility of T‐cell vaccination as well as conventional immunosuppression in the murine model of experimental autoimmune hepatitis (EAH). EAH was induced in 5‐ to 7‐week‐old BALB/c mice by immunization with syngeneic liver homogenate in complete Freund's adjuvant. For T‐cell vaccination, splenocytes were removed from animals 14 days after induction of EAH and from control animals, and activated in vitro by mitogen stimulation with Concanavalin A (Con A). Activated T cells were irradiated and injected at 5 × 10 7 cells per animal as T‐cell vaccine. Immunosuppression in control animals was performed with prednisolone with or without azathioprine. T‐cell vaccination with T cells from EAH animals, but not with irrelevant T cells, was able to protect animals from EAH, reducing the average disease severity from 2.2 (±0.3) to 0.5 (±0.3) ( P < .01). T‐cell vaccination was also able to treat EAH, because application of the vaccine 2 weeks after induction of the disease significantly reduced disease activity at week 4 from 2.4 (±0.4) to 1.1 (±0.2) ( P < .05). Both passive transfer of disease and the capacity to protect by T‐cell vaccination was mediated by CD4 T cells. Specific cellular recognition of activated disease‐inducing T cells could be detected in vaccinated animals. Immunosuppressive drugs could also suppress EAH. Thus, T‐cell vaccination in EAH is feasible and effective. Stimulation of a regulatory T‐cell network is the likely mechanism of action by which T‐cell vaccination can suppress EAH.