Education of human lymphocytes against mouse cells: specific recognition of H‐2 antigens

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Abstract
Xeno‐sensitization of human peripheral blood lymphocytes (PBL) against mouse lymphoid cells has been studied in vivo in a local graft‐vs. ‐host (GVH) assay and in vitro in a mixed lymphocyte culture‐cell‐mediated lympholysis system. Human PBL were injected into the footpads of mice rendered unresponsive by total‐body irradiation, and these were subsequently tested for the presence of cytotoxic cells in the draining popliteal lymph node (LN). In spite of a definite PBL‐induced LN proliferation, no cytotoxic activity was detected against mouse target cells. In contrast with the GVH assay, human PBL collected after 7 days of in vitro culture in the presence of irradiated mouse cells, were strongly cytotoxic against mouse target cells. The antigenic specificities recognized by in vitro educated cells were primarily those coded for by the H‐2 complex. Only target cells with an H‐2 haplotype identical to that of the sensitizing mouse strain or with at least an H‐2 D end in common with that strain were killed by xeno‐sensitized lymphocytes. Mouse target cells derived from congenic resistant strains remained unaffected. It was verified that in vitro educated PBL depleted of B cells retained their cytotoxic effect, indicating that non‐B cells and probably T cells were involved in the response.