The immunosuppressive human placental ferritin subunit p43 is produced by activated CD4+ lymphocytes

Human placental ferritin is an immunosuppressive protein composed of a 43-kDa subunit (p43) and ferritin light chains. Its physiological action seems to be downregulation of the immune response of the mother against her embryo. Elevated levels of p43 in serum are associated with pregnancy, lymphomas, breast cancer, and AIDS. Although it is known that p43 is produced by activated T lymphocytes, the specific T-lymphocyte subset involved is unknown. p43 is measured by enzyme-linked immunosorbent assays with CM-H-9 monoclonal antibody specific for p43. We studied the de novo biosynthesis of p43 by isolated activated CD4+ and CD8+ T lymphocytes in a normal donor and in a patient with elevated levels of p43 in serum. The results indicated that p43 was synthesized by activated CD4+ lymphocytes from the normal donor (0.45% of the total de novo proteins) but that its biosynthesis by CD8+ lymphocytes was below the level of detection. The activated CD4+ lymphocytes from the patient with elevated levels of p43 in serum overproduced p43 (3.8% of the nascent proteins). Since it was shown that a subset of CD8+ lymphocytes has receptors for p43, the latter may be considered an immunoregulatory cytokine produced mainly by activated CD4+ lymphocytes.