An investigation into the immunomodulatory activities of human placental protein 14 (PP14).

PP14 has been shown to suppress the incorporation of [3]H-Thymidine into both mitogenically and allogeneically stimulated lymphocytes in a dose dependent manner. The suppressive activity was shown to be specific, in that PP14 did not affect cellular viability, nor interact with the mitogen phytohaemagglutinin (PHA). Flow cytometric analysis indicated that PP14 had no effect on the expression of the Tac antigen, the transferrin receptor or HLA-DR molecules on the surface of stimulated lymphocytes. Neither did PP14 affect the interaction of interleukin-2 (IL-2) with its cell surface receptor. The suppressive activity was partially reversed by the addition of exogenous IL-2. PP14 inhibited the production of IL-2 from mitogenically stimulated lymphocytes and led to a small, but significant reduction in soluble IL-2 receptor release. Radiolabel binding studies and IL-2 dose response curves indicated that PP14 affected the affinity of the IL-2 receptor on PHA stimulated lymphocytes. This was supported by the observation that PP14 increased the level of cell surface-associated IL-2 on stimulated lymphocytes. There was a small inhibition of gamma interferon levels early in the culture period. PP14 had no effect on the CD4/CD8 ratio following stimulation and was not found to be associated with the cell surface, nor mask cell surface expression of the CD2 antigen.These data suggest that the immunosuppressive activity of PP14 may, in part, be mediated via a modulation of the functional, high affinity IL-2 receptor. It is not known as yet whether such an activity is effective at the level of induction of the receptors or whether the primary control is at another level of the response. PP14 may have implications in the study of implantation and fertility and prove of wider interest in the field of transplantation biology and the control of the immune response.