Improved long-term graft outcome in lung transplant recipients who have donor antigen-specific hyporeactivity

We have shown that in renal transplant recipients the development of in vitro donor antigen-specific hyporeactivity correlates with improved long-term graft outcome. Donor antigen-specific hyporeactivity is determined by in vitro mixed lymphocyte culture assays with recipient cells used as responder cells and homozygous typing cells as stimulator cells. Hyporeactivity is defined as a decreased response to stimulation by specific homozygous typing cells that define donor antigens, whereas response to homozygous typing cells defining third-party antigens remains unchanged. We tested 23 lung transplant recipients at least 1 year after transplantation to determine if donor antigen-specific hyporeactivity and the corresponding improved graft outcome were organ specific. Of these 23 recipients, eight had donor antigen-specific hyporeactivity; they demonstrated a trend toward a lower incidence of late acute rejection episodes (one rejection episode in one patient) versus the 15 recipients who remained responsive to donor antigens (11 rejection episodes in six patients). No recipients with donor antigen-specific hyporeactivity have been diagnosed with obliterative bronchiolitis, unlike six recipients who remained responsive to donor antigens (0% versus 40%; p = 0.058). We conclude that immune regulation, as evidenced by donor antigen-specific hyporeactivity, correlates with improved graft outcome for lung transplant recipients and may even provide immunologically based criteria for selecting candidates whose immunosuppression might be reduced successfully.