Survival-promoting activity of IL-7 on IL-2-dependent cytotoxic T lymphocyte clones: resultant induction of G1 arrest.
Interleukin-7 (IL-7) is essential for both T cell and B cell development. Recent studies have suggested that IL-7 also functions as a survival-promoting factor for resting and activated T cells. In this study we examined the effects of IL-7 on survival and cytotoxicity of tumor-specific CD8(+) cytotoxic T lymphocyte (CTL) clones established and maintained either with IL-2 alone or with a combination of IL-2 and IL-7. While the CTL clones cultured in IL-2 alone died around day 10, the CTL clones cultured in the presence of IL-2 and IL-7 survived for more than 4 weeks after seeding. The long-term survival of the latter was correlated with the presence of IL-7 in the medium. In addition, IL-7 alone prolonged survival of other IL-2-dependent CTL clones after the removal of IL-2. IL-7 maintained the CTLs in G1 arrest after a slight proliferation during the initial phase during which low-level but sustained DNA synthesis was observed. However, there was no direct correlation between DNA synthesis and enhancement of long-term survival by IL-7 as demonstrated by the inhibiting proliferation of the CTL clones with the protein kinase inhibitor genistein. During long-term survival in the presence of IL-7, the cytotoxic activities of the CTL clones decreased gradually to background levels although they were restored soon after the next passage. These results suggested that IL-7 had the ability to set machinery in motion against apoptosis in the IL-2-dependent CTL clones. Such an effect of IL-7 might play a role in vivo in the process leading activated T cells to the resting, that is, memory state.
Tsuda
K
K
Department of Bioregulation, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, Japan.
Toda
M
M
Kim
G
G
Saitoh
K
K
Yoshimura
S
S
Yoshida
T
T
Taki
W
W
Waga
S
S
Kuribayashi
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D015851:Interleukin-7; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D054353:Perforin; D004247:DNA