Interleukin‐2‐producing helper T lymphocyte precursors (HTLp) in the recipient recognize donor alloantigen expressed by the transplanted organ. The frequency of these reactive cells in the peripheral blood was determined and correlated with rejection episodes. Endomyocardial biopsy is generally used to quantify cardiac allograft rejection and guide immunotherapy. While non‐invasive techniques have been investigated, none of these has demonstrated sufficient sensitivity or specificity to replace myocardial biopsy. Twelve cardiac transplant recipients were assessed over a 1 year period using limiting dilution analysis, to determine the frequency of HTLp in response to cadaver donor splenocytes. The IL‐2‐dependent mouse cell line CTLL‐2 was used to measure the IL‐2 present and the precursor frequency was calculated using maximum likelihood estimation. In the months immediately post transplantation, six of the 12 recipients displayed an association with increases in HTLp frequency, which preceded histologically detectable rejection. The second six recipients had fewer rejection episodes and achieved ‘acceptance’ of their graft sooner. Once ‘acceptance’ was achieved, the association between IL‐2 HTLp frequency and rejection was no longer apparent. The ability to identify two groups of patients on the basis of IL‐2 HTLp frequency clearly highlights the heterogenous nature of the response to the graft and this emphasizes the need to monitor other cytokines, which may influence the functioning of effector T cells.

Background. Despite the current level of sophistication of molecular typing for class I and class II alleles, a significant proportion (20-40%) of recipients of HLA-identical sibling marrow develop severe, acute graft-versus-host disease (GVHD) after bone marrow transplantation, It has been suggested that the frequency of patient-specific helper T lymphocyte precursors (HTLp) detected in the HLA-identical sibling donor correlates with the incidence and severity of acute GVHD after transplantation.Methods. This study group consisted of 42 patients who all received bone marrow from HLA-identical sibling donors from January 1990 to December 1996. Using a limiting dilution analysis, donor HTLp frequencies were determined on samples collected before transplantation. The HTLp assay used the cytotoxic T-cell line, CTLL-2, which proliferates in the presence of interleukin-2. The reliability and reproducibility of this assay was established by using cryopreserved batches of CTLL-2 cells of known sensitivity.Results. The recipient-directed HTLp frequencies detected in the donor before transplantation were correlated with the incidence and severity of acute GVHD experienced by the recipient after transplantation. Statistical analysis revealed an extremely significant correlation between donor precursor frequencies and the development of acute GVHD in the patient after transplantation (P<0.0001).Conclusions. This study suggests that together with molecular typing the HTLp frequency should be considered when selecting the most suitable sibling donor for bone marrow transplantation.