Study on the Inhibition of the Immune Response of the Neonatal Rat Spleen by the Azathioprine Administered during Pregnancy

Abstract

The following experiment was performed to study the inhibition mechanism of the immune response in the neonatal rat spleen by azathioprine administered during pregnancy. The experimental animals were the two hundred neonatal rats which were born by sixty normal Sqrague- Dawley pregnant rats, of which 45 rats 8mgjkg of azathioprine were administered to orally at the 7th gestational day. Above two hundred experimental animals were divided into 6 groups as follows: Group 1: Neonatal rats to which T-dependent antigen, Sheep Red Blood Cells (SRBC) were injected intraperitoneally, born by normal pregnant rats. Group 2: Neonatal rats to which SRBC were injected intraperitoneally, born by pregnant rats to which azathioprine had already been given orally during pregnancy. Group 3: Neonatal rats to which SRBC were injected intraperitoneally and thymus cells derived from outbred neonatal rats were injected intravenously, born by pregnant rats to which azathioprine had already been given orally during pregnancy. Group 4: Neonatal rats to which T-independent antigen, Dextran was injected intraperitoneally, born by normal pregnant rats. Group 5: Neonatal rats to which Dextran was injected intraperitoneally, born by pregnant rats to which azathioprine had already been given orally during pregnancy. Group 6: Neonatal rats to which Dextran was injected intraperitoneally and thymus cells derived from outbrcd neonatal rats were injected intravenously, born by pregnant rats to which azathioprine had already been given orally during pregnancy. Antigen was injected intraperitoneally to above each group on the 1th, 8th and 12th weeks after birth and then, the spleen was resected on the 3rd and 7th days after injection of antigen for the plaque assay and histochemical studies. The following results were obtained: 1. Many plaque-forming cellsCPFC) were observed on the 3rd day after injection of antigen in all groups to which SRBC were injected, while many PFC were observed on the 7th day after injection of antigen in all groups to which Dextran was injected. 2. More PFC were observed in Group 1 than Group 2, and much more PFC were observed in Group 3. 3. There were no significant differences in number of PFC between Dextran·Groups(Group 4, Group 5 and Group 6). 4. There was strong tendency to recover the immunoIogicaI function with increasing age in SRBC· Groups(Group 1, Group 2 and Group 3). 5. Above results were in good accordance with those of histochemical observations. 6. It is strongly suggested that administration of azathioprine during pregnancy did suppress the development of fetal thymus, and that as a result of that suppression peripheral Tvhelper cells were depleted and consequently the formation of antibody was inhibited due to the insufficient colla' boration between T cells and B cells