High frequencies of cytotoxic T cell precursors against minor histocompatibility antigens after HLA-identical BMT: absence of correlation with GVHD

Limiting dilution analysis was used to quantify the frequency of cytotoxic T cell precursors (CTLp) against minor histocompatibility (H) antigens induced by HLA-identical BMT. The development of CTLp was monitored serially in ten patients developing either acute (n = 3), acute and chronic (n = 4) or no (n = 3) GVHD. In blood samples of patients taken shortly after BMT (< 100 days) a high frequency of anti-recipient CTLp was found (mean 1/3433). With time, this value decreased to become undetectable (< 1/500,000) beyond 400 days. This occurred also in patients still suffering from chronic GVHD. In contrast, autologous BMT did not induce any measurable recipient-reactive CTLp at any time point after BMT. In the early phase of reconstitution after BMT the frequency of CTLp against allo HLA-antigens was measured in the same patients. The absence of a consistent increase of allo-specific CTLp indicates that the kinetics of CTLp against host minor H antigens does not merely reflect an overall changed cytolytic potential shortly after BMT. These results indicate that: (1) HLA-identical BMT induces high frequencies of minor H antigen-specific CTLps detectable in the blood during the early phase of reconstitution, and (2) the frequency of recipient-reactive CTL measured in the peripheral blood is not an adequate parameter for GVHD. These data therefore challenge the clinical value of in vitro measurement of recipient-reactive CTLs in the peripheral blood after HLA-identical sibling BMT.