The role of viral and cell-associated antigens in the cell-mediated immune response of rats to virus-induced lymphoma cells.

Abstract

Induction of the cytotoxic cell response to rat syngeneic MuLV[murine leukemia virus]-induced lymphoma cells by viral and cell-associated antigens was evaluated. Priming of the immune response to lymphoma cells was dependent upon cell-associated antigens, since only lymphoma cells, and not purified virus, were able to prime memory CTL [cytotoxic T (thymus-derived) lymphocytes] precursors in vivo. In contrast, this dependency on cell-associated antigens was not observed upon secondary in vitro stimulation of spleen cells from lymphoma-primed rats. In this instance, purified virus and lymphoma cells had the capacity to induce a secondary CTL response against lymphoma cells. Further studies revealed the secondary CTL response to result from interaction between distinct T cell populations. These components were identified through the use of monoclonal antibodies against a rat differentiation antigen expressed by T cells (W3/13) and a T cell subset (W3/25). Although purified T cells developed a strong cytotoxic response, separated T cells of the W3/25+ or W3/25- subset did not. Mixtures of the W3/25- cells with W3/25+ cells generated CTL in a synergistic manner. Mixtures of W3/25- cells with mitomycin-inactivated cells from virus primed rats also generated CTL synergistically. The antilymphoma response consisted of at least 2 components. A population of noncytolytic cells, which responded to viral proteins, were apparently helper cells involved in the induction of CTL from a 2nd subset of W3/25- cells that were primed against lymphoma cell-associated antigens.