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Abstract
The antigenic specificity of a lymphocyte antifibroblast cellular immune reaction was studied in vitro. Rat lymphocytes were sensitized in vitro against foreign rat or mouse fibroblasts. Sensitized lymphocytes were then transferred to target monolayers of fibroblasts antigenically identical with, or unrelated to, the sensitizing fibroblasts. Injury to target cells was measured by the release of a radioactive label ( 51Cr). It was found that injury to antigenically unrelated target fibroblasts consistently occurred, although injury to antigen-specific fibroblasts was usually three- to sixfold greater. To test the ability of specific antigen to activate the lymphocyte cytolytic mechanism, target monolayers were prepared which contained mixtures of unlabeled antigen-specific and 51Cr-labeled antigenically unrelated fibroblasts. It was found that the interaction of sensitized lymphocytes with antigen-specific fibroblasts augmented the cytolytic effect against unrelated fibroblasts. The role of specific antigens in activating cytolysis was further studied by incubating target fibroblasts with specific antiserum. Antibodies were found to inhibit lymphocyte-mediated cytolysis in two distinct ways: they prevented antigen-dependent activation of lymphocytes by binding to specific fibroblast antigens, and they acted as a physical barrier to contact between activated lymphocytes and target cells. These results suggest that the destruction of target fibroblasts by sensitized lymphocytes proceeds in two stages. The first stage appears to be immunospecific and comprises the activation of the cytolytic effector by an interaction between lymphocytes and specific antigens. The second stage—the action of the cytolytic effector mechanism itself—does not seem to be immunospecific. Activated lymphocytes appear to be capable of injuring any fibroblasts, including syngeneic, with which close contact is made.
Published Version
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