Cellular immunity in the mouse. II. Correlation of in vivo and in vitro phenomena

A series of in vitro assays for lymphoid responsiveness to antigen (PPD) and allogeneic cells are described using the mouse model. The state of in vivo responsiveness measured by delayed hypersensitivity to PPD and allograft survival are compared to the in vitro assays of antigen-mediated lymphocyte proliferation (AMR), mixed lymphocyte proliferation (MLC), macrophage inhibition factor (MIF) activity release, and macrophage aggregation factor (MAF) activity release. These specific in vitro phenomena correlated only grossly in degree with the actual state of delayed hypersensitivity or allograft survival when measured statically. There was, however, a definite temporal relationship displayed during development of the phenomena. In vivo sensitization resulted in transient augmentation of in vitro response and the apparent development of immunologic memory. Antigen-mediated proliferation and augmentation of the MLC following sensitization were more transient than MIF activity release, perhaps indicating that different cell populations are responsible for the two types of in vitro events. The results also suggest that the ability to produce MIF activity is a prerequisite for in vivo responsiveness. The mixed lymphocyte response produced a substance(s) in the supernatant fluid which, when injected in vivo, resulted in a typical delayed hypersensitivity response. This supernatant also possessed MIF activity.