Carrageenans, highly sulfated polysaccharides and macrophage-toxic agents: newly found human T lymphocyte mitogens.

We obtained the following results, using carrageenans (CGNs) of three types (kappa, lambda and iota), macrophage-toxic agents. 1. CGNs were toxic to human monocytes, cytotoxicity varying from 40% to 60%, as judged by trypan blue dye exclusion test. 2. CGNs were proved to be newly found mitogens for human T cells, whereas CGNs are polyclonal B-cell activators in mice and induced DNA synthesis that peaked at days 6 or 7. In addition, iota CGN induced an early peak of 3H-thymidine uptake at day 1, which found out to be cytoplasmic uptake of 3H-thymidine. 3. Only lambda and iota CGN induced slightly higher DNA synthesis in purified B cells, but both failed to induce polyclonal antibody synthesis in B cells. 4. In spite of the fact the CGNs are macrophage-toxic agents, CGNs could induce Il-1 production by the surviving monocytes. Thus CGN-induced human T-cell activation requires a relatively smaller number of monocytes. 5. The mitogenic responses of T cells induced by kappa, lambda and iota CGN were significantly inhibited by cyclosporin A (CyA) treatment (250 ng/ml) and Con A and PHA responses were also inhibited by CyA addition. It was concluded that CGNs were newly found human T-cell mitogens, which is in sharp contrast with polyclonal B-cell activators in mice, and the mechanism of T-cell activation induced by CGNs was the same as that by Con A or PHA, though there may be another possibility of inhibition mechanism by CyA.