IFN-gamma: a cytokine essential for rejection of CTL-resistant, virus-infected cells.
We recently demonstrated differential susceptibility of cells expressing viral antigen to killing by antigen-specific cytotoxic T lymphocytes (CTLs). In addition, interferon-gamma (IFN-gamma) has been implicated in the clearance of some viruses from tissues. We explored the role of IFN-gamma in the cytotoxicity of Sendai virus-specific CTLs against virus-infected RL(male symbol)1 (T cell leukemia) or Meth A (fibrosarcoma) cells, as well as the growth of subcutaneously (s.c.) transplanted, virus-infected cells in IFN-gamma(+/+) or IFN-gamma(/) mice of the syngeneic strain (BALB/c). Sendai virus-specific CTLs were cytotoxic against virus-infected RL(male symbol)1 cells, and s.c. transplanted, virus-infected RL(male symbol)1 cells were acutely rejected from IFN-gamma(+/+) or IFN-gamma(/) mice. In contrast, the CTLs were inactive toward virus-infected Meth A cells, but s.c. transplanted, virus-infected Meth A cells were acutely rejected from IFN-gamma(+/+) but not IFN-gamma(/) mice. The s.c. growth of virus-infected Meth A cells in the mutant mice was markedly inhibited by s.c. injections of IFN-gamma, and the rejection from IFN-gamma(+/+) mice was delayed after specific elimination of macrophages by intravenous (i.v.) injections of dichloromethylene diphosphonatecontaining liposomes. These results suggest an essential role of IFN-gamma and involvement of macrophage in the rejection of CTL-resistant, virus-infected cells.
Yamaguchi
Satoko
S
Department of Physiology, Osaka Medical College, Takatsuki 569-8686, Japan.
Tashiro-Yamaji
Junko
J
Lee
Koutetsu
K
Takahashi
Takeshi
T
Sano
Kouichi
K
Endo
Yasuo
Y
Nakanishi
Mahito
M
Eguchi
Akiko
A
Okada
Masashi
M
Nomi
Hayahito
H
Yamamoto
Yumiko
Y
Takenaka
Hiroshi
H
Kubota
Takahiro
T
Yoshida
Ryotaro
R
D000818:Animals; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D006084:Graft Rejection / Q000276:immunology* / Q000821:virology; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D007371:Interferon-gamma