ORGAN-SPECIFIC PATTERNS OF DONOR ANTIGEN-SPECIFIC HYPOREACTIVITY AND PERIPHERAL-BLOOD ALLOGENEIC MICROCHIMERISM IN LUNG, KIDNEY, AND LIVER-TRANSPLANT RECIPIENTS

Although their relative importance and interaction are unclear, donor antigen(Ag)-specific hyporeactivity and allogeneic microchimerism hav e been associated with improved long-term graft outcome and a lower in cidence of chronic rejection in solid organ transplant recipients. We have postulated that a critical level of donor antigen, for a critical time period, is necessary to develop and maintain donor antigen-speci fic hyporeactivity; both the level and the time may differ by organ tr ansplanted. In our current study, we tested donor antigen specific hyp oreactivity and peripheral blood allogeneic microchimerism in liver an d kidney recipients and compared these values with our previous findin gs in lung recipients, We tested 25 liver recipients at 12 to 29 month s posttransplant: 10 (40%) had developed donor antigen-specific hypore activity; 5 (20%), peripheral blood allogeneic microchimerism. For all but 1 of the chimeric and hyporeactive recipients, the level of donor cells was very low (<1:20,000). Five hyporeactive recipients and all 15 donor antigen-responsive recipients did not have detectable levels of peripheral blood microchimerism. No chronic rejection has developed in any of these recipients to date-however, a lower incidence of acut e rejection was observed for those recipients with donor antigen-speci fic hyporeactivity (30% versus 60% without) or with peripheral blood a llogeneic microchimerism (20% versus 55% without) (P=ns), These result s differ from our previous findings in 19 lung recipients: at 12 to 18 months posttransplant, 35% of them had developed donor antigen-specif ic hyporeactivity; 47%, peripheral blood allogeneic microchimerism. Al l donor antigen-specific hyporeactivity recipients as well as some don or antigen-responsive recipients had peripheral blood allogeneic micro chimerism. We expanded our current study to include 26 recipients and a quantitative estimate of the level of allogeneic microchimerism. We observed that the hyporesponsive recipients tended to have higher leve ls of donor cells in their peripheral blood (>1:6,000) than did the re sponsive recipients. We previously reported that 22% of kidney recipie nts had developed donor antigen-specific hyporeactivity at 12 to 18 mo nths posttransplant. In our current study of 33 kidney recipients, we observed peripheral blood allogeneic microchimerism in 7 (21%) at 12 t o 18 months posttransplant, The level of donor cells was very low (sim ilar to 1:75,000), with no correlation between donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism at the t ime point tested, These studies emphasize the organ-specific nature of the development of donor antigen-specific hyporeactivity and the pers istence of peripheral blood allogeneic microchimerism. Donor antigen-s pecific hyporeactivity correlates with very low levels of donor cells in liver recipients, while a higher critical level of donor cells is i mportant in lung recipients. Additional sequential early posttransplan t studies are necessary to further define the possible interrelationsh ip between donor antigen and the development and maintenance of donor antigen-specific hyporeactivity.