Immunosuppressive factors released by transforming lymphocytes in the delayed hypersensitivity skin response to tuberculin.

Experiments were carried out in BCG-sensitized cattle to see if factors produced by transforming blood lymphocytes could modify the tuberculin skin reaction or the uptake of [3H]thymidine by sensitized bovine lymphocytes. It was found that the subcutaneous injection on one side of the neck of tuberculin, tuberculin-stimulated autologous blood lymphocytes or culture supernates from tuberculin-stimulated lymphocytes depressed the response to intradermal injection of tuberculin on the other side. The suppression of the response appeared to be antigenically specific since the delayed skin reaction to the intradermal injection of brucallergen was not suppressed by the injection of the same lymphocyte culture supernates. In vitro studies of [3H]thymidine uptake by autologous lymphocytes showed that the culture supernates from tuberculin-stimulated lymphocytes had a mitogenic activity, but at higher concentrations of supernate, this mitogenic activity was depressed. The higher concentration of supernate also non-specifically suppressed [3H]thymidine uptake by autologous lymphocytes stimulated with phytohaemagglutinin or brucallergen. Since an immunosuppressive α-globulin fraction had been demonstrated in bovine serum by other workers, it was thought that this may have been the factor released in vitro by the transforming lymphocytes. The α-globulin fraction was therefore isolated from sera of four tuberculous cattle, obtained 10 days after tuberculin skin testing, and from four uninfected and untested control cows. This serum α-globulin fraction from both groups of cattle, suppressed [3H]thymidine uptake by homologous lymphocytes stimulated with tuberculin or PHA but levels of this factor in sera of tuberculous cattle were not raised above those in control cattle. It was concluded that the antigenically-specific suppression of tuberculin skin-reactions was most likely mediated by antigen—antibody complexes. On the other hand results with cultured lymphocytes may have been due to a non-specific immunosuppressant released from lymphocytes and which had properties in common with a serum α-globulin fraction.