Sequential interaction of macrophages, initiator T lymphocytes and recruited T lymphocytes in a cell-mediated immune response to soluble antigen.

We have investigated the sequential interaction of macrophages, initiator T lymphocytes (ITL) and recruited T lymphocytes (RTL) in the development of a T cell-mediated response to soluble antigens. Macrophages were pulsed with soluble antigens and used to sensitize ITL in vitro. The ITL were irradiated to prevent their proliferation and then injected into the footpads of syngeneic mice. Sensitized ITL were found to recruit immunospecific RTL in the draining lymph nodes, as determined by a thymidine uptake assay of the lymph node cells in vitro. The richest source of lymphocytes with ITL activity was the thymus, and progressively less activity was detectable among spleen or lymph node lymphocytes. The magnitude of the subsequent RTL response could be modified by genetic differences between the ITL and the antigen-pulsed macrophages that were used to sensitize them. Thus, ITL conveyed an immunogenic signal to RTL whose magnitude reflected the genotype of the macrophages, but whose specificity was directed by determinants of the soluble antigen.