Submitted on December 16, 2003
Accepted on August 8, 2004
Immunoglobulin Treatment Suppressed Adoptively Transferred Autoimmune Myocarditis in Severe Combined Immunodeficient (SCID) Mice
Keisuke Shioji, Zuyi Yuan, Toru Kita, and Chiharu Kishimoto*
* To whom correspondence should be addressed. E-mail: kkishi{at}kuhp.kyoto-u.ac.jp.
We investigated the suppressive effects of immunoglobulin (Ig) upon effector T cells in autoimmune myocarditis. Treatment with Ig reduced the production of the so-called 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 into severe combined immunodeficient (SCID) recipients was successfully achieved. Treatment with Ig, but not with F(ab')2 fragments of immunoglobulin, reduced the mortality and the severity of myocarditis in SCID recipient mice. Decreased ability of LN cells of Ig-treated rats, but not of F(ab')2 fragments-treated rats, to transfer autoimmune myocarditis was also demonstrated. The findings of present study suggested that autoimmune myocarditis was successfully transferred into SCID mice and that treatment with Ig ameliorated autoimmune myocarditis with inducing selective myosin unresponsiveness via the Fc portion resulting in suppression the Th1 cytokine production and the cytotoxic activities of LN cells, which operated together in the development of autoimmune myocarditis.
