MEASUREMENT OF RECIPIENT-SPECIFIC ALLOREACTIVITY - IS GVHD PREDICTABLE

Acute graft-versus-host disease (GVHD) is a serious complication of al logeneic bone marrow transplantation (BMT) from an HLA-identical sibli ng. There is no practical test before transplantation that gives suffi cient information to predict the degree of allogeneic reactivity betwe en HLA-identical siblings. We determined the frequency with which host -specific interleukin-2 (IL-2) -secreting donor T lymphocyte precursor s (Tl-p) occurred in 16 pairs of HLA-identical siblings before they un derwent marrow grafting. The results were correlated with the developm ent of acute GVHD after BMT. We further analyzed the responding host ( and donor) -specific Tl-p with respect to the cell surface phenotype, the influence of previous in vivo priming, and the MHC class restricti on of minor histocompatibility (mH) antigen recognition. To investigat e whether host-reactive Tl-p are involved in the induction of acute GV HD, we also examined the frequency of host-specific Tl-p at various ti me intervals after BMT in 14 patients with and without acute GVHD. Hig h frequencies of host-specific Tl-p were detectable before BMT in 8 do nors whose siblings later had severe (grade II or III) acute GVHD. Amo ng the donors to 8 patients with mild (grade 0 or I) acute GVHD, low f requencies were found. Various T-cell subsets contributed to the respo nding Tl-p. The presence of host-specific Tl-p after BMT was significa ntly correlated with the development of serious (grade II or III) acut e GVHD. We conclude that host-specific IL-2-secreting T cells are crit ically involved in the induction and maintenance of acute GVHD. Analys is of the frequency of such cells before BMT may be a useful predictor of severe acute GVHD in allogeneic BMT between HLA-identical siblings . Patients at risk for serious acute GVHD may be identified before BMT and assigned alternative immunosuppressive regimens.