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In vitro analysis of the cellular interactions between unprimed lymphocytes responsible for determining the class of response an antigen induces: specific T cells switch a cell-mediated response to a humoral response.

Unprimed murine spleen cells, when cultured at different densities but in the presence of the same concentration of antigen, are induced to mount different classes of response. Three modes of behavior are found. A low density does not support the induction of any response, a medium density supports a transient IgM and substantial delayed-type hypersensitivity (DTH) response, and a high density only supports a sustained IgM response. This in vitro system has been used to show that a low density of cells, when complemented with irradiated specific T cells, can mount a DTH response, and thus behave as a medium density of cells. These observations show that the induction of DTH requires helper T cells, and that a medium density, in contrast to a low density, allows sufficient collaboration to obtain a DTH response. The observation that a high density only mounts a sustained humoral response suggests that the formation of more helper T cell-dependent signals than the number generated at a medium density may be required to induce a sustained humoral response as well as the suppression of DTH. This hypothesis is supported by the findings that the response by a medium density of cells is dramatically affected by the addition of irradiated antigen-specific helper T cells; the DTH response is specifically suppressed and a sustained humoral response is observed. These results show that the induction of a humoral response is more T cell dependent than the induction of a cell-mediated response and provides an in vitro means for switching a cell-mediated response to a humoral one in an antigen-specific manner. Observations are also presented to show that the production of antibody by a high density of cells is not a prerequisite for the suppression of DTH reactivity.