A stable form of delayed-type hypersensitivity.

An antigen dose below the level needed to provoke an antibody response produces in mice a persistent, but minor degree of delayed-type hypersensitivity (dth) to sheep red blood cells. The DTH is unstable. It is erased by larger doses of antigen and cannot be built upon by further antigenic stimulation. The much higher levels of DTH resulting from immunization under the modulating influence of cyclophosphamide (CY) or BCG persist under strong secondary antigenic stimulation, though the former is subject to partial suppression unless CY is used to prevent the secondary humoral response. The DTH produced by a BCG-modulated primary response is not subject to this suppressive effect of a secondary antibody response. In this case the anamnestic T-cell response is very brisk and cannont be potentiated by giving CY at the time of the secondary antigenic stimulus. This effect is not due to the modulating influence of a residual BCG infection. It results from a permanent change induced during the primary response. The mediator cells formed under the influence of BCG are apparently resistant to inhibition by blocking serum containing immune complexes. Even the actively dividing T cells which are susceptible to vinblastine, and most readily blocked in the absence of BCG, are highly resistant to blocking by immune complexes. It is not clear whether these cells are intrinsically different or whether their insensitivity to blocking results from features peculiar to the humoral response that accompanies a BCG-modulated primary response. The mediator cells produced by both BCG- and CY-modulated responses become vinblastine resistant, relatively insensitive to humoral blocking factors, and capable of surviving in a functionally active form in syngeneic recipients with an apparent half-life of about 50 days. There were indications, however, that their effective life-span may be greatly extended in some circumstances by persisting antigenic stimulation; and in the case of BCG-modulated immunity the prevailing level of T-cell activity can be greatly augmented by a further antigenic stimulus without the necessity for renewed exposure to BCG.