Natural cytotoxic reactivity of rat lymphocytes against gross virus-induced tumor cell lines as measured by [125I]iododeoxyuridine and tritiated proline microcytotoxicity assays.

Mononuclear cells from rat spleens that mediate "natural" cytotoxicity are described, and the subpopulation responsible for this activity is partially identified. These naturally cytotoxic cells have been designated "N-cells" and appear to be lymphocytes that lack both detectable immunoglobulin and complement receptors and are therefore not mature B-cells. They are different from the classic "null cells", which have immunoglobulin and/or complement recepters. This subpopulation of cells is responsible for the natural activity present is normal spleens and in spleens from immunized animals. These results indicate that the same subpopulation of cells responsible for natural activity in the short-term assays is also responsible for natural activity in the long-term microcytotoxicity assays reported here. In addition, these mononuclear cells are active against both nonadherent cells and monolayer targets. Natural activity as measured by the long-term assays appears to be somewhat less age specific than that reported previously with the short-term chromium assay. Appropriate base lines are described in an attempt to better document natural activity in these assays. This natural activity must be closely monitored in any system purporting to measure cell-mediated cytotoxicity.