Studies on the resistance to tolerance induction against human IgG in DDD mice. II. Tolerogen-resistant T-cell population in the spleen.

Further studies were carried out to investigate cellular sites of the resistance to the induction of immunological tolerance to HGG in DDD mice, assuming the presence of a subset of tolerogen-resistant splenic T cells. Spleen-seeking T cells were shown to be relatively resistant in comparison with lymph node-seeking T cells. The existence of a tolerogen-resistant T-cell subpopulation was indicated from the experiments demonstrating that tolerance was easily attained after adult thymectomy and that lymph node T cells became much more resistant to tolerance induction after adult splenectomy. The latter experimental result might also exclude the possibility of differences in microenvironment (probably in A cells) between spleen and lymph node. An attempt was made to investigate a possible involvement of A cells in the induction of tolerance. A cells were deprived in vivo by irradiation of the host 3 days prior to spleen cell transfer and in vitro by passing a spleen cell suspension through a Sephadox G-10 column. The deprivation of A cells resulted in priming of the host by the tolerogen rather than easier tolerance induction. No suppressive activity was observed in lymph node cells from tolerized mice. These results suggest that there exists a set of T cells, generated relatively recently in the thymus, preferentially migrating into spleen and there becoming resistant to tolerance induction.