Primed CTLs specific for HLA class I may still be present in sensitized patients when anti-HLA antibodies have disappeared: relevance for donor selection.

Background. The presence of donor-specific HLA antibodies is generally considered to be a contraindication for transplantation, even when these antibodies are only present in historical sera. Previous studies showed that donor-specific antibodies in current sera were associated with the presence of primed cytotoxic T cells (CTLs) with a high avidity for donor HLA class I antigens. The presence of these CTLs is considered to be a reflection of an activated immune systems and a contraindication for transplantation with a donor sharing these particular HLA antigens. Methods. In the present study we compared the incidence of primed CTLs in patients with anti-HLA antibodies in current sera and in patients with anti-HLA antibodies in historical sera only. Cytotoxic T lymphocyte precursor (CTLp) frequencies and the incidence of primed CTLs directed against HLA class I antigens to which the patient had formed antibodies were studied in 37 sensitized renal patients. As controls, antigens to which a patient has never formed antibodies were tested. Results. In patients with antibodies in current sera mainly primed CTLs were detected, whereas in patients where the antibodies had disappeared mainly naive CTLs were detected. However, in four patients primed CTLs persisted despite the fact that the HLA antibodies had disappeared, Conclusion. Considering the previously described association between primed CTLs and graft rejection, these findings may be relevant for the selection of patients who can be transplanted across a positive historical crossmatch. If the antibodies have disappeared and only naive CTLs are present, a successful transplantation should be feasible. A prospective study will reveal whether this is indeed the case.