Immunoglobulin treatment suppressed adoptively transferred autoimmune myocarditis in severe combined immunodeficient mice.
We investigated the suppressive effects of immunoglobulin (Ig) on effector T cells in autoimmune myocarditis. Treatment with Ig reduced production of the so-called T-helper type 1 (Th1) cytokines stimulated by concanavalin A or cardiac myosin in cultured lymph node (LN) cells from rats with myocarditis. The cytotoxic activities of LN cells from rats immunized with myosin and treated with Ig were reduced against cardiomyocytes and F-2 cells compared with those treated without Ig. The adoptive transfer of myocarditis from LN cells of Lewis rats with myocarditis to severe combined immunodeficient (SCID) recipients was successfully achieved. Treatment with Ig, but not with F(ab')2 fragments of Ig, reduced the mortality and severity of myocarditis in SCID recipient mice. Decreased ability of LN cells of Ig-treated rats, but not rats treated with F(ab')2 fragments, to transfer autoimmune myocarditis was also demonstrated. The findings of the present study suggest that autoimmune myocarditis was successfully transferred to SCID mice and that treatment with Ig ameliorated autoimmune myocarditis by inducing selective myosin unresponsiveness via the Fc portion, resulting in suppression of Th1 cytokine production and cytotoxic activities of LN cells, which operated together in the development of autoimmune myocarditis.
Dept. of Cardiovascular Medicine, Graduate School of Medicine, Kyoto Univ., 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Keisuke
K
Shioji
Zuyi
Z
Yuan
Toru
T
Kita
Chiharu
C
Kishimoto
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D016207:Cytokines / Q000096:biosynthesis; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009205:Myocarditis / Q000276:immunology* / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D007140:Immunoglobulin Fab Fragments; D016756:Immunoglobulins, Intravenous