Expansion of human T-cell leukemia virus type 1 (HTLV-1) reservoir in orally infected rats: inverse correlation with HTLV-1-specific cellular immune response.
Adult T-cell leukemia (ATL) occurs in a small population of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals. Although the critical risk factor for ATL development is not clear, it has been noted that ATL is incidentally associated with mother-to-child infection, elevated proviral loads, and weakness in HTLV-1-specific T-cell immune responses. In the present study, using a rat system, we investigated the relationships among the following conditions: primary HTLV-1 infection, a persistent HTLV-1 load, and host HTLV-1-specific immunity. We found that the persistent HTLV-1 load in orally infected rats was significantly greater than that in intraperitoneally infected rats. Even after inoculation with only 50 infected cells, a persistent viral load built up to considerable levels in some orally infected rats but not in intraperitoneally infected rats. In contrast, HTLV-1-specific cellular immune responses were markedly impaired in orally infected rats. As a result, a persistent viral load was inversely correlated with levels of virus-specific T-cell responses in these rats. Otherwise very weak HTLV-1-specific cellular immune responses in orally infected rats were markedly augmented after subcutaneous reimmunization with infected syngeneic rat cells. These findings suggest that HTLV-1-specific immune unresponsiveness associated with oral HTLV-1 infection may be a potential risk factor for development of ATL, allowing expansion of the infected cell reservoir in vivo, but could be overcome with immunological strategies.
Hasegawa
Atsuhiko
A
Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Ohashi
Takashi
T
Hanabuchi
Shino
S
Kato
Hirotomo
H
Takemura
Fumiyo
F
Masuda
Takao
T
Kannagi
Mari
M
D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015481:HTLV-I Antibodies / Q000097:blood; D015486:HTLV-I Antigens / Q000008:administration & dosage / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D011533:Proviruses; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
D004279:DNA, Viral; D015481:HTLV-I Antibodies; D015486:HTLV-I Antigens