1990 Fiscal Year Final Research Report Summary
Pathogenic Role of T Cell Mediated Cytotoxicity on Fibroblasts in Dermatomyositis
| Project/Area Number |
63570303
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | Toho University |
|---|
Principal Investigator |
SAITO Eizou Toho University, School of Medicine Assist. Prof., 医学部, 助教授 (10112690)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ARAKI Hiroshi Toho University, School of Medicine, Resident, 医学部, 助手 (80120228)
|
|---|
| Project Period (FY) |
1988 – 1990
|
| Keywords | dermatomyositis / polymyositis / fibroblast / mononuclear cell / cytotoxic T lymphocyte / cytokinesis / glucocorticoid / malignancy |
|---|
| Research Abstract |
Head Investigator : #493610112690, Eizo Saito, Toho Uninv., Department of Medicine, Assistant Professor
Investigator : #471180120228, Hiroshi Araki, Toho Uninv., Department of Medicine, Assistant
The effect of peripheral mononuclear cells (MNC) from patients with dermatomyositis (DM) on cultured human skin fibroblasts was studied and the following results were obtained ; (1) When human skin fibroblasts were incubated with DM MNC, striking attachment of MNC around fibroblasts was observed. Cell proliferation of fibroblasts after incubation was significantly deppressed. ^<51>Cr releasing study demonstrated that DM MNC possess dominant cytotoxic activity on fibroblasts. (2) The damaging effects of DM MNC were specific to fibroblasts. It was also specific to DM MNC, and MNC from other subjects including polymyositis patients did not show such effect. (3) Effector cells were T8 positive lymphocytes. The presence of monocytes was essential. (4) Attachment of MNC to fibroblasts was an important
… More
step. (5) When DM lymphocytes and normal monocytes were added to fibroblasts, the cytotoxicity was observed, whereas no cytotoxicity was observed when normal lymphocytes and DM monocytes were added. (6) The cytotoxicity was inhibited by anti-IL-2 antibody, but not by anti-IL-1 and anti-IL-6 antibodies. In the presence of the conditioned medium obtained from DM MNC culture, normal MNC showed the cytotoxicity on fibroblasts. When normal MNC were stimulated with IL-2, these cells also gained cytotoxic activity on autologous and allogenic fibroblasts. Consequently, IL-2 seems to play an important role. (7) Glucocorticoids inhibited the cytotoxicity in a dose-response manner. (8) MNC from DM patients with malignancy showed the cytotoxicity on fibrlblasts. It was completely lost after treatment and the malignancy resolved. Contrarily, MNC from uncomplicated DM patients continued to show cytotoxicity even when they were in inactive stage. Then, in patients with DM and malignancy, the primary lesion seems to be malignancy. Results of the present study strongly suggest that DM is a disease which is mediated by the autoimmune cytotoxic T lymphocyte reaction against interstitial tissues. Less
|
