Definitive engagement of cytotoxic CD8 T cells in C protein-induced myositis, a murine model of polymyositis.
OBJECTIVE
To substantiate a pathogenic role of cytotoxic CD8 T cells in the development of a murine polymyositis model, C protein-induced myositis (CIM).


METHODS
Beta(2)-microglobulin-null mutant, perforin-null mutant, and wild-type (WT) C57BL/6 mice were immunized with skeletal muscle C protein fragments to provoke CIM. Regional lymph node CD8 or CD4 T cells stimulated with C protein-pulsed dendritic cells were transferred adoptively to naive mice. Inflammation and damage of the muscle tissues were evaluated histologically.


RESULTS
The incidence of myositis development was significantly lower in β₂-microglobulin-null and perforin-null mutant mice compared with WT mice. Inflammation was less severe in mutant mice, and the incidence of muscle injury was reduced significantly. Adoptive transfer of lymph node T cells from mice with CIM induced myositis in naive recipient mice. The CD8 T cell-induced muscle injuries were significantly more severe than the CD4 T cell-induced muscle injuries.


CONCLUSIONS
Perforin-mediated cytotoxicity by CD8 T cells is definitively responsible for muscle injury in CIM.
Sugihara
Takahiko
T
Tokyo Medical and Dental University, Tokyo, and Yokohama Institute, RIKEN, Yokohama, Japan.
Okiyama
Naoko
N
Suzuki
Mihoko
M
Kohyama
Kuniko
K
Matsumoto
Yoh
Y
Miyasaka
Nobuyuki
N
Kohsaka
Hitoshi
H
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017285:Polymyositis / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000276:immunology*
D052899:Pore Forming Cytotoxic Proteins; D001613:beta 2-Microglobulin; C483886:perforin, mouse