Frequency analysis of donor-reactive cytotoxic T lymphocyte precursors in in allograft recipients. Lack of correlation with clinical outcome

The frequency of donor-reactive and of third party-reactive cytotoxic T lymphocyte precursors (CTLp) was determined by limiting dilution analysis in the peripheral blood of 13 liver allograft recipients before (pre-tpx) and at various intervals (4 to 22 months) after (post-tpx) transplantation. In 6 of 13 patients with stable graft function, no change of donor-reactive CTLp occurred within 9 to 17 months post-tpx, and high levels of donor-reactive CTLp (frequencies ranging from 1/1024 to 1/13,295) were maintained. In contrast, a 4-11-fold reduction of donor-reactive CTLp frequencies was observed in 5 patients within 4 to 22 months post-tpx; in 3 of these patients the measured frequency of donor-specific CTLp dropped to biologically irrelevant levels (1/43,800 to 1/150,000). However, a 5-7-fold increase of the post-tpx frequency of donor-reactive CTLp was observed in two additional patients with stable graft function. Taken together, these results demonstrate that the frequency analysis of donor-reactive CTLp in the peripheral blood does not closely correlate with the clinical outcome. Thus, stable liver allograft function after > 1 year of transplantation can be associated with a specific deletion, unaltered levels, or even an increase in the frequency of circulating donor-reactive CTLp.