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 v irus type 1 (HTLV-1) infection. In this study, we demonstrated that HTLV-1- transformed tumors could develop in immunocompetent rats by blocking a cost imulatory signal for T-cell immune responses, Four-week-old WKA/HKm rats we re treated with monoclonal antibodies (MAbs) to CD80 and CD86 and subcutane ously inoculated with syngeneic HTLV-1-infected TARS-1 cells, During MAb tr eatment for 14 days, TARS-1 inoculation resulted in the development of soli d tumors at the site of inoculation, which metastasized to the lungs. In co ntrast, rats not treated with MAbs promptly rejected tumor cells. Splenic T cells from MAb-treated rats indicated impairment of proliferative and cyto toxic T-lymphocyte responses against TARS-1 in vitro compared to untreated rats. However, tumors grown in MAb-treated rats regressed following withdra wal of MAb therapy. Recovery of TARS-1-specific T-cell immune responses was associated with tumor repression in these rats. Our results suggest that H TLV-1-specific cell-mediated immunity plays a critical role in immunosurvei llance against HTLV-1-transformed tumor development in vivo.