In vitro CTL precursor frequencies do not reflect a beneficial effect of cross-reactive group (CREG) matching

Adjustment of histocompatibility-based allocation criteria in kidney transp lantation from HLA matching to matching on the basis of cross-reactive grou ps (CREG), was recently suggested to be a good alternative to transplant wi th more "well-matched" kidneys, without negatively influencing graft surviv al. Because graft rejection is often mediated by cytotoxic T cells (CTLs), we investigated whether a beneficial effect of CREG matching is reflected i n vitro by lower CTL precursor frequencies (CTLpf). Therefore, CTLpf were d etermined in a group of healthy individuals and analyzed with respect to th e number of HLA and CREG mismatches. A clear correlation was found between the number of HLA mismatches and the CTLpf, that is, the lowest mean freque ncy in case of 0 HLA-A, B mismatches (66 CTL precursors per 10(6) cells) an d che highest in combinations with 4 HLA mismatches (mean 303 CTLp/10(6) ce lls). The situation was different in the case of CREG mis-marches. Although the highest frequency was found in the group of 4 CREG mismatches, no sign ificant differences were observed between 0, 1, and 2 CREG mismatches. High CTLpf, up to 430/10(6), were even seen in the case of 0 CREG mismatches. A lso within a well-defined group of single HLA-A or HLA-B mismatches no diff erence in CTLpf were observed between the subgroups with 0 vs. 1 CREG misma tches. The present study showed chat in vitro the CTLpf correlates better w ith HLA than with CREG matching. These data are consistent with findings re ported by several groups chat matching for the CREG does not benefit transp lant outcome. Human Immunology 61: 879-883 (2000). (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.