Allogeneic microchimerism and donor antigen-specific hyporeactivity in lung transplant recipients

The identification of peripheral donor cells in solid organ transplant recipients has led to speculation as to the tolerogenic role of circulating donor cells. Also being debated is the possible significance of persistent donor alloantigen-presenting cells in inducing and maintaining an alloantigen-specific unresponsive state. Previously, we showed that donor antigen-specific hyporeactivity is a useful marker for identifying kidney, lung, or heart recipients at low risk for immunologic complications; we found donor antigen-specific hyporeactivity in 25% of kidney, 35% of lung, and 22% of heart recipients. All 3 hyporeactive subgroups experienced fewer late (> 3 months) rejection episodes and a lower incidence of chronic rejection. The purpose of the current study was to determine whether peripheral blood microchimerism correlates with the development of donor antigen-specific hyporeactivity and affects clinical outcome. We correlated the detection of microchimerism with in vitro proliferative response to donor antigen in 19 lung recipients who were ≥ 12 months posttransplant. Allogeneic peripheral blood microchimerism was studied with a PCR-based limiting detection assay using HLA-DR sequence-specific primers. We detected microchimerism in 47% (9 of 19) of the lung recipients tested. All recipients who were donor antigen-specific hyporesponsive had microchimerism, and all recipients without detectable microchimerism were responsive to donor antigen. However, not all recipients with microchimerism developed donor antigen-specific hyporeactivity. Further, none of the hyporesponsive recipients has been diagnosed with obliterative bronchiolitis (OB). In contrast, 2 of the 4 with microchimerism who were responsive to donor antigen have been diagnosed with OB, as have 5 of the 10 who were negative for both hyporeactivity and microchimerism. Thus, long-term graft outcome may correlate more closely with donor antigen-specific hyporeactivity than with microchimerism.