Immunological aspects of rat models of HTLV type 1-infected T lymphoproliferative disease.
The level of host immune responses against human T cell leukemia virus type 1 (HTLV-1) varies among HTLV-1-infected individuals. In the present study, we investigate the role of host immunity on HTLV-1 leukemogenesis in vivo by using animal models. At first, we examined the effect of the routes of HTLV-1 transmission on the host anti-HTLV-1 immune responses. When immune competent adult rats were inoculated with HTLV-1-infected cells, the orally infected rats were persistently infected with HTLV-1 without humoral and cellular immune responses against HTLV-1, whereas all intravenously or intraperitoneally inoculated rats showed significant levels of immune responses. Next, we examined in vivo tumorigenicity of HTLV-1-immortalized cells in the absence of T cell immunity, by using athymic F344/N Jcl-rnu/rnu (nu/nu) rats. When inoculated into nu/nu rats, not all but some HTLV-1-immortalized rat cell lines including syngeneic FPM1-V1AX could grow and form T cell lymphoma in vivo. This syngeneic lymphoma formation was inhibited by adoptively transferred immune T cells. Furthermore, immunocompetent rats allowed in vivo growth of HTLV-1-infected lymphoma, when treated with antibodies that block costimulatory signals for T cell activation. These observations indicated that (1) host anti-HTLV-1 immunity can be affected by the conditions of the primary infection, (2) under the low pressure of anti-HTLV-1 immunity, some HTLV-1-infected cell clones grow in vivo, and (3) T cell immunity is required for in vivo surveillance against these HTLV-1-infected cell clones.
Kannagi
M
M
Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, Tokyo 113, Japan. kann.impt@med.tmd.ac.jp
Ohashi
T
T
Hanabuchi
S
S
Kato
H
H
Koya
Y
Y
Hasegawa
A
A
Masuda
T
T
Yoshiki
T
T
D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004195:Disease Models, Animal; D015481:HTLV-I Antibodies / Q000097:blood; D015490:HTLV-I Infections / Q000276:immunology / Q000635:transmission / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
D015481:HTLV-I Antibodies