Repression of tax expression is associated both with resistance of human T-cell leukemia virus type 1-infected T cells to killing by tax-specific cytotoxic T lymphocytes and with impaired tumorigenicity in a rat model.
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL). Although the viral transactivation factor, Tax, has been known to have apparent transforming ability, the exact function of Tax in ATL development is still not clear. To understand the role of Tax in ATL development, we introduced short-interfering RNAs (siRNAs) against Tax in a rat HTLV-1-infected T-cell line. Our results demonstrated that expression of siRNA targeting Tax successfully downregulated Tax expression. Repression of Tax expression was associated with resistance of the HTLV-1-infected T cells to Tax-specific cytotoxic-T-lymphocyte killing. This may be due to the direct effect of decreased Tax expression, because the Tax siRNA did not alter the expression of MHC-I, CD80, or CD86. Furthermore, T cells with Tax downregulation appeared to lose the ability to develop tumors in T-cell-deficient nude rats, in which the parental HTLV-1-infected cells induce ATL-like lymphoproliferative disease. These results indicated the importance of Tax both for activating host immune response against the virus and for maintaining the growth ability of infected cells in vivo. Our results provide insights into the mechanisms how the host immune system can survey and inhibit the growth of HTLV-1-infected cells during the long latent period before the onset of ATL.
Nomura
Machiko
M
Department of Immunotherapeutics, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Ohashi
Takashi
T
Nishikawa
Keiko
K
Nishitsuji
Hironori
H
Kurihara
Kiyoshi
K
Hasegawa
Atsuhiko
A
Furuta
Rika A
RA
Fujisawa
Jun-ichi
J
Tanaka
Yuetsu
Y
Hanabuchi
Shino
S
Harashima
Nanae
N
Masuda
Takao
T
Kannagi
Mari
M
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D016356:Gene Products, tax / Q000235:genetics / Q000502:physiology*; D016355:Genes, pX; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology / Q000235:genetics / Q000276:immunology; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D004279:DNA, Viral; D016356:Gene Products, tax; D000949:Histocompatibility Antigens Class II; D034741:RNA, Small Interfering; D015375:Receptors, Interleukin-2