Th1-type immune responses by Toll-like receptor 4 signaling are required for the development of myocarditis in mice with BCG-induced myocarditis.
The immunological aspects of autoimmune myocarditis are difficult to understand because of the existence of many infectious agents and animal models suggesting different mechanisms in autoimmune myocarditis. To overcome these difficulties, two strains of mice, C3H/HeN and C3H/HeJ, showing different immune responses to mycobacteria, were immunized with myosin mixed with BCG. The C3H/HeN mice with a wild-type Toll-like receptor 4 (TLR4) showed severe myocarditis, whereas the C3H/HeJ mice with nonfunctional mutated TLR4 did not. CD4(+) cells from both strains of mice exhibited appreciable proliferative responses following myosin stimulation; however, the cytokines from these cells differed between these two strains. The C3H/HeN mice showed T helper (Th)1-type cytokine responses, whereas the expressions of mRNA in C3H/HeJ mice were Th2-type cytokine. When both of these strains of immunized mice were inoculated with a plasmid encoding cDNA of interleukin (IL)-4 or agonistic IL-4, the development of myocarditis was inhibited in C3H/HeN mice. Moreover, C3H/HeJ mice, in which development of myocarditis was not induced by immunization of myosin mixed with BCG, showed myocarditis after injection of IL-4 antagonistic mutant DNA for the induction of Th1-type immune responses. The results suggested that the induction of autoimmune myocarditis by myosin is affected by Th1-type immune responses.
Nishikubo
Kimiaki
K
Department of Rheumatology, National Hospital Organization, Mie Chuo Medical Center, Mie 514-1101, Japan.
Imanaka-Yoshida
Kyoko
K
Tamaki
Shigenori
S
Hiroe
Michiaki
M
Yoshida
Toshimichi
T
Adachi
Yukihiko
Y
Yasutomi
Yasuhiro
Y
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009163:Mycobacterium bovis / Q000276:immunology; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009218:Myosins / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D015847:Interleukin-4; D009218:Myosins