Rejection of a kidney transplant does not always lead to priming of cytotoxic T cells against mismatched donor HLA class I antigens.

BACKGROUND: Previous studies showed that graft rejection is often associated with the presence of primed cytotoxic T cells (CTLs) with a high avidity for donor cells. Similar high avidity CTLs have been found in individuals who have formed IgG anti-HLA antibodies. The presence of such CTLs to a specific HLA mismatch is therefore considered to be a reflection of an activated immune system, and a contraindication for retransplantation with a donor sharing this particular HLA class I mismatch. METHODS: In our study we investigated whether patients have always primed CTLs against all individual HLA class I mismatches present on a rejected graft. Therefore, 14 patients who had undergone transplantectomy after irreversible kidney graft rejection were analyzed with respect to donor-specific CTLp frequencies and the presence or absence of high avidity CTLs directed against HLA class I mismatches present on the rejected graft. RESULTS: Patients, who have not formed anti-HLA antibodies against the donor have mainly naive CTLs. Most of the patients, that have developed IgG anti-HLA antibodies against a donor mismatch, have primed CTLs directed against that particular mismatch. However, patients with IgM anti-HLA antibodies only, and patients with IgG anti-HLA antibodies in historical sera but no IgG anti-HLA antibodies in current sera, have mainly naive CTLs against the donor HLA mismatch. CONCLUSION: Our results suggest that it is not always necessary to exclude repeated HLA class I mismatches for a subsequent transplantation. In addition to good anti-HLA antibody screening, the CTLp-assay may be a useful tool for donor-selection in retransplant candidates.

Pregnancy can induce long-persisting primed CTLs specific for inherited paternal HLA antigens.

Previous studies showed that pregnancy can prime the maternal cellular immune response directed against paternal HLA antigens. Primed CTLs specific for inherited paternal HLA antigens (IPA) were found in women who had formed HLA allo antibodies, whereas naive CTLs were present in women who did not form antibodies against the paternal HLA antigens. As HLA allo antibodies may disappear in time, it is not clear which women on the waiting list for transplantation have been sensitized to paternal HLA antigens and are at risk for graft rejection if paternal HLA antigens are shared by the donor organ. The presence of primed CTLs specific for a particular antigen is considered to be a reflection of sensitization.In the present study we investigated whether these primed CTLs persist in women who had been pregnant and had formed antibodies against the inherited paternal HLA class I antigens. For this purpose 14 women who had their last pregnancy 10 years ago were analyzed with respect to IPA-specific CTLp frequencies and the presence of high avidity CTLs directed against inherited paternal HLA class I antigens. Although primed CTLs specific for IPA's were found more frequently in women with persisting alloantibodies, they still can be detected when the antibodies have disappeared. The current data show that primed CTLs directed against inherited paternal HLA antigens towards which antibodies have been formed in the past can persist for more than 10 years after pregnancy. The cellular test used in our study can be useful to detect presensitization in women with a history of pregnancy, who enter the waiting list for transplantation.