Development of human T-cell leukemia virus type 1-transformed tumors in rats following suppression of T-cell immunity by CD80 and CD86 blockade.
Host immunity influences clinical manifestations of human T-cell leukemia virus type 1 (HTLV-1) infection. In this study, we demonstrated that HTLV-1-transformed tumors could develop in immunocompetent rats by blocking a costimulatory signal for T-cell immune responses. Four-week-old WKA/HKm rats were treated with monoclonal antibodies (MAbs) to CD80 and CD86 and subcutaneously inoculated with syngeneic HTLV-1-infected TARS-1 cells. During MAb treatment for 14 days, TARS-1 inoculation resulted in the development of solid tumors at the site of inoculation, which metastasized to the lungs. In contrast, rats not treated with MAbs promptly rejected tumor cells. Splenic T cells from MAb-treated rats indicated impairment of proliferative and cytotoxic T-lymphocyte responses against TARS-1 in vitro compared to untreated rats. However, tumors grown in MAb-treated rats regressed following withdrawal of MAb therapy. Recovery of TARS-1-specific T-cell immune responses was associated with tumor regression in these rats. Our results suggest that HTLV-1-specific cell-mediated immunity plays a critical role in immunosurveillance against HTLV-1-transformed tumor development in vivo.
Hanabuchi
S
S
Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, Japan.
Ohashi
T
T
Koya
Y
Y
Kato
H
H
Takemura
F
F
Hirokawa
K
K
Yoshiki
T
T
Yagita
H
H
Okumura
K
K
Kannagi
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D002455:Cell Division / Q000276:immunology; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy / Q000821:virology*; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D007376:Interleukin-2; D008562:Membrane Glycoproteins