The use of nonspecific T acceptor cells to overcome the aberrant function of antigen-specific third-order T suppressor cells

Earlier studies in the phenyltrimethylamino (TMA) hapten system demonstrated that under certain conditions idiotype-specific second-order T suppressor (Ts2)-bearing mice fail to suppress TMA-specific delayed-type hypersensitivity. This was due to a functional deletion in the third-order T suppressor (Ts3) subset. In this report we have confirmed and extended these findings to show that only homologous TMA-specific Ts3 can restore suppressor function, both heterologous Ts3 and unprimed T-cell populations failed to do so. Furthermore, attempts to induce Ts3 function in the defective mice after reconstitution with normal precursor Ts3 cells also failed. In contrast, protocols which induce heterologous contact and cutaneous hypersensitivity reactions readily induced cell populations capable of restoring suppression in the Ts3-defective mice. Analysis of the lymphoid populations from the contact-sensitized defective mice revealed that these cells were not the prototypical Ts3 but were similar to the previously reported nonspecific T acceptor cell. The results further indicated that the T acceptor cell functioned as the active terminal-phase Ts subset, and this could be used as an alternative to the TMA-specific Ts3. The importance of multiple suppressor pathways at the terminal phase of immune suppression is discussed.