The Tolerization Of Rat Thymocytes To Xenogeneic Erythrocytes - Kinetics Of Induction And Recovery

The intravenous injection of large doses of xenogeneic erythrocytes into rats completely abrogated the ability of thymocytes from such animals to provide help for antierythrocyte antibody responses in an adoptive transfer system. Thymocyte tolerance developed at a time when the thymocyte donors were producing antibody to the tolerizing antigen, and spleen helper T cells were not tolerized by the injection protocol. A minimum of two injections of 1 ml of packed erythrocytes, spaced 4 - 5 days apart, was required to induce loss of helper activity. Tolerance was fully developed within 16 h of the last injection of antigen. Helper activity recovered over a 24-h period starting 5 days after this injection but could be delayed by giving further injections of antigen. These results suggest that the intrathymic pool of cells with assayable helper activity turns over in about one day and that precursors of this pool are probably also tolerable. Suppressor cells could not be detected in tolerant thymocyte populations indicating that the loss of helper activity was either a consequence of clonal inactivation or that an antigen-specific mechanism existed for the recruitment of helper cells from the thymus. The significance of these findings to the acquisition of self-tolerance is discussed.