Effects of neonatal injections of anti-CD3 epsilon monoclonal antibodies on the T cell functions of adult mice.

The effect of neonatal injections of anti-CD3 mAb on the subsequent immune responsiveness of adult mice has been investigated. The data indicate that neonatal treatment with three injections of 50 microliters of anti-CD3 epsilon ascitic fluid induce a profound depletion of T cells in the peripheral lymphoid organs but do not modify the absolute number of thymocytes. This treatment completely abolishes the T cell functions of mice at least 3 wk after the last injection of mAb. In the thymus, this suppression is associated with a decrease in the number of TcR/CD3 molecules in the dull CD3+ cells and with a drastic reduction the bright CD3+ population. However, the amount and the size of the TcR alpha,beta and CD3 epsilon mRNA transcripts are not modified, suggesting that the down-regulation of the TcR/CD3 complex induced by anti-CD3 mAb does not exert a feedback inhibition on the transcription of TcR genes. The suppression induced by neonatal injections of anti-CD3 epsilon mAb is reversible and the induction of immune responses requires the reappearance of a minimal number of bright CD3+ cells. However, this suppression can be maintained without side effects for several months provided that anti-CD3 mAb were administered at 7-day intervals from birth. This injection schedule should allow the study of the effect of anti-CD3 antibodies during the T cell ontogeny on the establishment of the B and T cell repertoires.