Effect of PGE₁ treatment on in vitro thymocyte function of normal and autoimmune mice

Autoimmune New Zealand (NZ) mice exhibit a broad spectrum of T and B cell disorders. These include abnormally high levels of terminal deoxynucleotidyl transferase-positive immature T cells in bone marrow and thymus. We have shown previously that prostaglandin E₁ (PGE₁) treatment of the NZB/NZW F₁ hybrid, a murine model of systemic lupus erythematosus (SLE), reduces to normal the percentage of immature terminal deoxynucleotidyl transferase-positive cells in bone marrow and thymus, and prevents the immune complex-induced nephritis which kills these animals. We report here that short-term (1-5 days) treatment of NZB/W mice with PGE₁ increases thymocyte responsiveness to mitogens and alloantigens. The majority (> 90%) of cortical thymocytes agglutinated by peanut lectin (PNA⁺) are depleted by PGE₁ treatment. However, a small population of highly functional cells persists in the PNA⁺ fraction after PGE₁ treatment. PGE₁ appears to have little or no effect on the PNA-negative (medullary) fraction of thymocytes. Our data suggest that PGE₁ may exert its therapeutic effect in NZ mice by increasing the functional maturity of immature T cells.