Cell-Mediated Immune Response to Syngeneic UV-Induced Tumors

Abstract

Abstract An Ia-positive accessory cell with macrophage characteristics was demonstrated to be required for the in vitro proliferation and differentiation of lymph node T lymphocytes from tumor-immunized mice into cytotoxic T lymphocytes (CTL). An experimental system is described that provides for the measurement of both proliferation and CTL capacity in in vitro cultures of draining lymph node (DLN) cells from tumor-immunized mice. DLN cells obtained from the popliteal lymph nodes of mice immunized in the hind footpads with a syngeneic UV-induced fibrosarcoma proliferate and differentiate into highly effective CTL (as assessed in a 6-hr chromium release assay) when placed in culture without the addition of tumor antigen. Both proliferation and CTL generation by DLN cells in vitro were shown to result from the interaction of at least two physically separable cell populations: a T cell population responsible for the proliferation and expression of CTL activity, and an accessory cell population required for the expression of the T cell functions. The accessory cell was shown to be resistant to γ-radiation, adherent to nylon and glass wool columns, sensitive to treatment with anti-Ia antisera plus complement (C), and resistant to treatment with anti Thy-1 antisera plus C. Antigen presentation did not appear to be required for effective cooperation between lymphocytes from tumor-immunized mice and accessory cells, although antigen presentation did occur when unprimed lymphocytes were mixed with accessory cells present in the DLN of tumor-immunized mice. The regulation of CTL development and the role of the Ia-positive accessory cell in anti-tumor immunity are discussed.