PREGNANCY-ASSOCIATED, LYMPHOCYTE-DERIVED SUPPRESSOR FACTOR INHIBITS PROTEIN-KINASE-C ACTIVITY

For successful allogenic pregnancy to occur, suppression of maternal d efense responses toward the fetus are vital. Suppressor factors elabor ated by decidual cells or immune cells may facilitate this suppression . In order for appropriate cellular responses to occur an intact signa l transduction/second messenger system must be present. The calcium/ph ospholipid-dependent protein kinase, Pk-C, plays an important role in regulating immune responses, and may also be important in regulating u terine cell responses and implantation events. Pk-C activation is nece ssary for IL-2 synthesis and IL-2 receptor synthesis through activatio n of the proto-oncogenes c-jun and c-fos. These proto-oncogene gene pr oducts combine to form the heterodimer AP-1 which then activates IL-2 gene transcription for both peptide and receptor. If Pk-C activity bec omes abrogated then appropriate cell responsiveness is diminished. We have shown that Pk-C activity is decreased in the particulate fraction of 4-7 day pregnant spleen, thymus and draining lymph node (DLN) cell s. Spleen cells did not exhibit any change in cytosolic Pk-C activity, the thymus was found to have a decrease in both cytosol and particula te fractions, and the DLN cells exhibited a translocation effect where by particulate Pk-C decreased and cytosolic Pk-C activity increased. S upernatant from 3-day cultures of DLN cells from pregnant animals was shown to inhibit proliferation of spleen cells. In addition, the super natant was able to directly lower Pk-C activity. We hypothesize that D LN cells secrete a factor(s) that is able to suppress immune response through abrogation of Pk-C activity, thereby decreasing AP-1 formation resulting in decreased IL-2 synthesis and IL-2 receptor synthesis.