T-cell subsets, IFN-γ production and efferent specificity in anti-parental tumor immunity induced by mouse sensitization with xenogenized variant cells

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Abstract
In addition to previous evidence for a role of L3T4+ T cells in the protective anti‐parental tumor immunity induced by xenogenized variant cells of a murine lymphoma (L5I78Y/DTIC), we have investigated the possible participation in this effect of L5I78Y tumor‐specific lymphocytes of the Lyt‐2+ T cell subset. Spleen cells from L5178Y/DTIC tumor‐immunized mice produced high levels of IFN‐γ in vitro in response to parental antigens, and this activity was only abolished by treating the responder population with anti‐Thy‐1.2 antibody or a combination of anti‐L3T4 and anti‐Lyt‐2.2 monoclonal antibodies (MAbs) plus complement. Positively selected L3T4+ and Lyt‐2+ cells also produced IFN‐γ in vitro, provided accessory cells (plastic‐adherent and Thy‐I− Ia− splenocytes, respectively) were added to the lymphocyte‐tumor cell co‐cultures. The production of IFN‐γ by purified L3T4+ and Lyt‐2+ cells was inhibited by addition of the respective anti‐class‐II and anti‐class‐I H‐2 antibody to the cultures. Administration of anti‐IFN‐γ MAb in vivo significantly impaired the resistance of L5178Y/DTIC‐immune mice to challenge with parental cells, as manifested by survival criteria and increased tumor‐cell proliferation in the spleens of antibody‐treated mice. Although anti‐parental tumor protection in vivo and T‐cell activation in vitro for IFN‐γ production were strictly antigen‐specific, bystander tumor inhibition was observed when antigenically irrelevant cells were inoculated with the L5178Y lymphoma. These results suggest that both L3T4+ and Lyt‐2+ T cells play a role in the protective anti‐parental tumor immunity induced by xenogenized cells, and that their activity may involve IFN‐γ‐mediated stimulation of non‐specific tumoricidal mechanisms.