PREGNANCY CAN INDUCE PRIMING OF CYTOTOXIC T-LYMPHOCYTES SPECIFIC FOR PATERNAL HLA ANTIGENS THAT IS ASSOCIATED WITH ANTIBODY-FORMATION

Some transplant centers consider paternal HLA antigens as unacceptable mismatches for mothers awaiting kidney transplantation. It is feared that a pregnancy may cause priming of the maternal immune response dir ected toward paternal HLA antigens, Should a woman receive an organ fr om a donor who shares those paternal HLA antigens, the risk of graft r ejection might be increased, It is known that some women, as a consequ ence of pregnancy, develop antibodies specific for paternal HLA antige ns, The purpose of the present study was to investigate whether a preg nancy can also prime the cellular immune response and whether this occ urs in all cases. Frequencies of maternal cytotoxic T lymphocytes dire cted to paternal HLA antigens were evaluated in limiting dilution anal ysis assays and compared with those directed to third-party HLA antige ns, Differentiation between naive and in vivo primed cytotoxic T lymph ocytes was made by performing these assays in the absence and presence of anti-CD8, respectively. No difference in the frequency nor sensiti vity to blocking by anti-CD8 was found when maternal cytotoxic T lymph ocytes directed toward paternal HLA antigens were compared with those against third-party HLA antigens, However, more heterogeneous response s were detected against paternal HLA antigens. Therefore, paternal ant igens that had been inherited by children were analyzed separately fro m the paternal antigens that had not been inherited. Furthermore, the presence of pregnancy-induced HLA antibodies was taken into considerat ion, Naive cytotoxic T lymphocyte responses were detected against pate rnal antigens that had never been inherited and those that had been in herited but had not induced antibody formation, In contrast, inherited paternal antigens that had induced HLA-specific antibodies in the mot her gave rise to elevated cytotoxic T lymphocyte precursor frequencies , as compared with the response to third-party antigens, Also, the cyt otoxic T lymphocytes were found to be more resistant to inhibition by anti-CDS, suggesting that these cells had been primed in vivo. These r esults suggest that not all paternal HLA antigens have to be considere d as unacceptable mismatches, Only those individuals who share a pater nal HLA antigen against which a mother has formed HLA-specific alloant ibodies should be excluded from organ donation.