T-helper-cell-specific monoclonal antibody inhibits growth of B-cell lymphomas in syngeneic SJL/J mice

Transplantable follicular center cell lymphomas of SJL/J mice are B-cell tumors that stimulate proliferation of host T-helper (TH) cells and which grow progressively in the peripheral lymphoid tissues of immunocompetent recipients. However, tumor growth is compromised in immunosuppressed syngeneic recipients, suggesting that the host response to SJL follicular center cell (SJL/FCC) lymphoma cells is required for optimal tumor growth. In vitro studies indicate that the host TH cells (Lyt-1+, 2-, L3T4a+) which respond to the major histocompatibility complex (MHC) class II (I-As) surface determinants on the SJL/FCC lymphoma cells produce a variety of lymphokines, some of which may promote tumor growth in vivo. The results of this study demonstrate that treatment of lymphoma-injected mice with L3T4a-specific mAb inhibits the growth of the SJL/FCC lymphoma cells, despite the fact that these tumor cells do not express L3T4a determinants. Thus, in this model, mAb therapy targeting host immune cells rather than the tumor cells is an effective means to control tumor growth. Long-term observation of SJL/FCC lymphoma-injected, anti-L3T4a mAb-treated mice reveals prolonged survival of the majority of these animals with periodic recurrence of tumor growth. During periods of remission, LN cells from these long-term surviving animals were unable to mount the characteristic in vitro host response to irradiated SJL/FCC lymphoma cells. These results provide direct evidence that SJL/FCC lymphoma cells fail to retain their characteristic neoplastic properties in a microenvironment that is initially devoid of tumor-responsive TH cells.