Cell interactions in the induction of tolerance: the role of thymic lymphocytes.

Thymectomized, lethally irradiated, bone marrow reconstituted mice were treated with a large dose of sheep red blood cells (SRBC) over the course of 30 days. They were unable to respond to further antigenic challenge for one month. Fifteen million thymocytes given 4 days after the termination of treatment restored their ability to respond. The same antigenic treatment given to similar chimeras, which differed only in having had 15 × 10 thymus cells added to the bone marrow inoculum, also abolished the response to further antigenic challenge. In contrast to chimeras without thymus cells present during the course of treatment, the later addition of thymocytes to these animals did not restore their response. It did, however, restore the response to a second challenge of antigen given 17 days after the addition of thymocytes. This response was the same as non-treated animals given only one injection of thymocytes and significantly less than non-treated animals given thymocytes twice. The following explanation of these results is offered. Bone marrow derived (BMD) lymphocytes that can make antibody without assistance of thymus derived (TD) lymphocytes were made tolerant in the absence of TD cells. Thymus dependent BMD cells were not. New cells, coming from the bone marrow, broke the tolerant state within a month. When TD cells were present both populations of BMD cells, as well as the TD cells, were made tolerant. New BMD cells regenerating from the bone marrow abrogated the tolerant state of the BMD population. This breaking of tolerance could only be seen in mice given additional thymocytes as the tolerance of the TD cells was not broken in the absence of a thymus. Thus, the induction of tolerance as well as the induction of immunity in thymus dependent BMD cell populations, seems to require the co-operation of TD cells.