RGD Reference Report - Regression of human T-cell leukemia virus type I (HTLV-I)-associated lymphomas in a rat model: peptide-induced T-cell immunity. - Rat Genome Database

RGD Reference Report - Regression of human T-cell leukemia virus type I (HTLV-I)-associated lymphomas in a rat model: peptide-induced T-cell immunity. - Rat Genome Database

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Regression of human T-cell leukemia virus type I (HTLV-I)-associated lymphomas in a rat model: peptide-induced T-cell immunity.
Authors:	Hanabuchi, S Ohashi, T Koya, Y Kato, H Hasegawa, A Takemura, F Masuda, T Kannagi, M
Citation:	Hanabuchi S, etal., J Natl Cancer Inst. 2001 Dec 5;93(23):1775-83. doi: 10.1093/jnci/93.23.1775.
RGD ID:	150527855
Pubmed:	PMID:11734593 (View Abstract at PubMed)
DOI:	DOI:10.1093/jnci/93.23.1775 (Journal Full-text)
BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) is etiologically linked to adult T-cell leukemia (ATL). The disease has a high mortality rate and is resistant to chemotherapy; therefore, immunologic approaches to treatment could be of interest. We have previously shown that athymic rats inoculated with a syngeneic (i.e., with the same genetic background) HTLV-I-infected T-cell line (FPM1-V1AX) develop ATL-like disease and that the transfer of T cells from normal syngeneic rats immunized with FPM1-V1AX cells prevents disease development. In this study, we further characterized the host antitumor immunity to explore the possibility of peptide-based vaccination against the ATL-like disease. METHODS: Immune T cells from rats immunized with FPM1-V1AX cells were analyzed for their phenotypes and cytotoxic properties. The epitope recognized by the T cells was analyzed by fine mapping. To evaluate the antitumor effects of a peptide-based vaccine, normal rats were immunized with synthetic oligopeptides corresponding to the epitope, the T cells were transferred to athymic rats inoculated with HTLV-I infected cells, and tumor size was monitored. RESULTS: Both CD4+ and CD8+ T-cell populations from rats immunized with FPM1-V1AX cells inhibited the growth of FPM1-V1AX cell-induced lymphomas in vivo. Long-term culture of splenic T cells from the immunized rats repeatedly resulted in establishment of CD8+ HTLV-I-specific cytotoxic T lymphocyte (CTL) lines restricted to the rat major histocompatibility complex class I molecule, RT1.A(l). The cytotoxicity of these lines was directed against the HTLV-I regulatory protein Tax and, specifically, against the epitope, amino acids 180-188 (GAFLTNVPY). Adoptive transfer of the Tax 180-188-specific CTL line or freshly prepared T cells from rats vaccinated with the Tax 180-188 oligopeptide prevented the development of FPM1-V1AX-cell induced lymphomas in athymic rats in comparison with control groups (two rats in each group). CONCLUSIONS: This study indicated a potential therapeutic effect of peptide-based vaccination against HTLV-I-induced lymphoproliferative disease.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Cd8a	Rat	cell surface		IDA			RGD

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Genes (Rattus norvegicus)

Cd8a (CD8 subunit alpha)

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