Long-term exposure to superantigen induces p27Kip1 and Bcl-2 expression in effector memory CD4+ T cells.
The long-term exposure of mice to superantigen SEA using a mini-osmotic pump (SEA pump) induced a long-lasting expansion of Vbeta3+ CD4+ T cells with T helper (Th) 2 cell-type properties. Removal of the SEA pump 10 days after pump implantation did not significantly alter the level of Vbeta3+ CD4+ T cell expansion/maintenance. Furthermore, CFSE-labeled CD4+ T cells failed to divide when transferred to post-implantation day 15 mice. Thus, CD4+ T cells appeared to survive for at least 30 days in the absence of a sufficient amount of antigen to trigger cell division. STAT6 deficient mice, in which Th2 cell development is largely impaired, also exhibited a protracted cell expansion, similar to that observed in normal mice, suggesting that the Th2 cell property is dispensable for the maintenance of Vbeta3+ CD4+ T cell expansion. The expanded CD4+ T cells on post-implantation day 26 were arrested in the G0/G1 phase of the cell cycle and showed a lower level of cell division upon restimulation. The Cdk inhibitor p27(Kip1) was highly expressed, and Cdk2 was downregulated. Moreover, the CD4+ T cells were resistant to in vitro apoptosis induction in parallel with their level of Bcl-2 expression. Collectively, the Vbeta3+ CD4+ T cells appeared to develop into long-lived memory T cells with cell cycle arrest upon long-term exposure to SEA.
Koyanagi
Madoka
M
Department of Microbiology and Immunology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Fukada
Kenji
K
Uchiyama
Takehiko
T
Yagi
Junji
J
Arimura
Yutaka
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis* / Q000235:genetics*; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics*; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D004768:Enterotoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D018089:Superantigens; D050760:Cyclin-Dependent Kinase Inhibitor p27; C026066:enterotoxin A, Staphylococcal