TNP-modified syngeneic cells enhance immunoregulatory T cell activities similar to allogeneic effects.

Abstract

Abstract The ability of TNP-modified syngeneic B cells (TNP-B cells) to alter unprimed T cell regulation of in vitro humoral immune responses to sheep erythrocytes was examined. High doses of T cells (>106) suppressed TNP-B cell activation, and irradiation of the T cells (1000 R) abolished this suppression, revealing a significant degree of radioresistant help in the T cell preparations. Similarly, help was enhanced when the T cells were irradiated and co-cultured with semiallogeneic B cells (Allo-B cells). T cells (<108) pretreated with mitomycin C provided a greater degree of help to both TNP-B cells and Allo-B cells than the untreated T cells; however, significant mitomycin C-resistant suppression was apparent with higher doses of T cells. In contrast to T cell regulation induced by TNP-B cells and Allo-B cells, help provided to unmodified syngeneic B cells was of lower magnitude and was relatively sensitive to irradiation and mitomycin C treatment, and suppressor activities were not as apparent. In “bystander” and “membrane-segregated” cultures TNP-modified B cells also augmented T cell activities with features similar to those stimulated by allogeneic cells. i) Irradiated, TNP-modified stimulator cells induced a significant degree of bystander help that was radioresistant. Allo-B cells also enhanced bystander help, although significant bystander suppressive effects also were apparent with high T cell doses. ii) The helper activity induced by TNP-B cells and Allo-B cells was mediated primarily by diffusible factors, and the production of the factors was radioresistant. iii) The release kinetics of the helper factors were similar, in that optimal helper activity was observed by 48 hr. In contrast, factor-mediated help observed with unmodified syngeneic cells was minimal and attained optimal levels at 72 to 96 hr. In conclusion, TNP-modified syngeneic B cells stimulated T cell activities, leading to the enhancement of nonantigen-specific help and suppression with characteristics similar to positive and negative allogeneic effects, respectively. This study indicates that immunoregulatory T cell function can be modulated by self-altering agents.