Regression of human T-cell leukemia virus type I (HTLV-I)-associated lymphomas in a rat model: peptide-induced T-cell immunity.
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.
Hanabuchi
S
S
Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8519, Japan.
Ohashi
T
T
Koya
Y
Y
Kato
H
H
Hasegawa
A
A
Takemura
F
F
Masuda
T
T
Kannagi
M
M
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines; D002460:Cell Line; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism* / Q000473:pathology*; D008223:Lymphoma / Q000517:prevention & control / Q000628:therapy* / Q000821:virology*; D008232:Lymphoproliferative Disorders / Q000517:prevention & control / Q000821:virology; D008285:Major Histocompatibility Complex; D051379:Mice; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D013601:T-Lymphocytes; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014611:Vaccination; D022223:Vaccines, Subunit / Q000737:chemistry; D014616:Vaccinia virus / Q000378:metabolism
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D000939:Epitopes; D010455:Peptides; D022223:Vaccines, Subunit