Distinct mitogens reveal different mechanisms of suppressor activity in human cord blood

We have studied the suppressive ability of human cord blood lymphoid cells in a three-days mixed lymphocyte culture proliferation assay stimulated by mitogen. Sex chromosomes served as markers for dividing cord (male) or maternal cells. Three distinct mitogenic agents were used in the co-cultures: the mitogenic lectin PHA, the anti-CD3 monoclonal antibody OKT3, and 12-0-tetradecanoyl-13-acetate (TPA), a direct activator of protein kinase C. With all mitogens we observed significant, non-specific suppression of maternal/adult cell division. However, three separate levels of suppression were evident. PHA-stimulated co-cultures always showed the highest amount of cold suppressor activity (mean +/- SEM: 64.9 +/- 3.9). The mean suppression in OKT3- and TPA-stimulated co-cultures was 34.7 +/- 6.0 and 22.0 +/- 4.1%, respectively. Furthermore, indomethacin, a prostaglandin (PG) synthetase inhibitor, reduced by 41% the suppression in PHA-driven co-cultures, whereas having no significant effect on the corresponding OKT3-driven co-cultures. Our results indicate the existence of an indomethacine-sensitive, PG-dependent mechanism and a separate, indomethacine-resistant, mechanism of cord cell suppression.