Apoptosis induction in human peripheral blood T lymphocytes by high-dose steroid therapy.
High-dose steroid pulse therapy is effective in transplant rejection and severe autoimmune diseases. Our goal was to identify the mechanism by which high-dose steroid exerts specific immunosuppressive actions. In this study, we investigated the in vivo effects of high-dose (1 g) methylprednisolone infusion on peripheral blood T lymphocyte apoptosis induction in 15 patients with severe autoimmune diseases. DNA fragmentation was detected in peripheral blood T cells isolated from these patients after 2 and 4 hr of steroid infusion. In contrast, T cells isolated from the same patients before or 8 or more hours after infusion did not show DNA fragmentation. DNA fragmentation was more significant in CD4+ than CD8+ T cells. The susceptibility of CD4+ T cells to apoptosis was associated with a lower expression of Bcl-2 in these cells compared with that on CD8+ T cells. To support the T-cell apoptosis induction by pulse therapy, peripheral blood T cells from normal subjects underwent DNA fragmentation after in vitro exposure to 2.5-10 microg/ml of methylprednisolone for 30 min. Our results indicate that induction of peripheral blood T-cell apoptosis is an important mechanism contributing to the immunosuppression observed after high-dose steroid therapy.
Migita
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Kawabe
Y
Y
Nakamura
T
T
Shirabe
S
S
Tsukada
T
T
Ichinose
Y
Y
Nakamura
H
H
Nagataki
S
S
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects*
D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D008775:Methylprednisolone