Studies on delayed hypersensitivity in mice. III. Evidence for suppressive regulatory T1-cell population in delayed hypersensitivity.

T-T-cell interactions involved in delayed hypersensitivity (DH) response have been studied by employing delayed foot pad assay to methylated human serum albumin in C57BL/6J mice. The DH response, one of the T-cell manifestations of cell-mediated immune response is suppressively regulated by T cells and such observation was based on studies of age-associated kinetics of foot pad reaction and effects of cell transfer and adult thymectomy on developing DH response. These suppressively regulatory T cells in DH have a life span of less than 4 wk and a constant derivation from the thymus is required. Such cells are numerous in the young mouse thymus and few in the spleen and thymus of old mice. On the one hand, the presence of a long-lived effector T-cell population was suggested in DH. These cells are numerous in the spleen and are low responders to phytohemagglutinin in vitro. It is assumed that these suppressive T cells interact with antigen-reactive cells at their proliferating stage by recognition of the iodiotypic difference through surface receptors. As in the case of graft-vs.-host and humoral response in vivo, three different subsets of immune competent cells participate in the DH response. These cells consist of one specifically antigen-reactive T cell, one suppressive regulatory T cell, and one bone marrow-derived cell, a macrophage that responds to a chemical mediator from sensitized effector T cells and that develops a DH skin lesion nonspecifically.