ADAPTIVE IMMUNE-RESPONSES DURING MURINE PREGNANCY - PREGNANCY-INDUCED REGULATION OF LYMPHOKINE PRODUCTION BY ACTIVATED T-LYMPHOCYTES

OBJECTIVE: We hypothesized that the lymphokine production by splenocytes and decidual lymphocytes would be altered because of changes in immunoregulation during pregnancy. STUDY DESIGN: Splenocytes and decidual lymphocytes were isolated from syngeneic and allogeneic pregnant mice at different times of gestation. The lymphocytes (10(7) cells/ml) were stimulated with anti-CD3 antibody, and culture supernatants were assayed for several lymphokines, including interleukin-2, interferon-gamma, interleukin-4, interleukin-6, granulocyte-macrophage colony-stimulating factor, and interleukin-3. Statistical analysis was by analysis of variance or paired t test. RESULTS: Activated splenocytes produced significantly less interleukin-2 and more interleukin-4, interleukin-6, and interleukin-3 as murine pregnancy advanced. Production of interferon-gamma and granulocyte macrophage colony-stimulating factor by activated splenocytes peaked in the first 8 to 14 days of pregnancy. Stimulated decidual lymphocytes produced modest amounts of interleukin-6, granulocyte-macrophage colony-stimulating factor, and interleukin-3 during pregnancy but no interleukin-2, interferon-gamma, or interleukin-4. Similar results were found for both syngeneic and allogeneic matings. CONCLUSIONS: Our findings indicate that splenocyte lymphokine production favors interleukin-4 production over interleukin-2 production. This finding suggests that antibody production would be enhanced and cytotoxic cellular immune responses inhibited during pregnancy. These changes occurred regardless of mating partner, suggesting that the specific antigenic stimulus during normal pregnancy does not regulate lymphokine production. Activated splenocytes and decidual lymphocytes were found to differ in their capacity to produce lymphokines, indicating that the decidua constitutes a distinct and unique immunologic microenvironment.