The role of in vitro alloreactive T-cell functional tests in the selection of HLA matched and mismatched haematopoietic stem cell donors.

Acute graft vs. host (GVH) disease and graft rejection are most frequently caused by undetected or disregarded genetically based disparities between the donor and recipient of bone marrow derived haematopoietic stem cells (HSC). Incompatibilities in extremely polymorphic human leukocyte antigens (HLA), and in certain cases also minor histocompatibility antigens, represent the most important driving force of such unwanted events, threatening the successful outcome of haematopoietic stem cell transplantation (HSCT). The complexity of HLA polymorphism can be precisely and elegantly detected at the genomic level by several polymerase chain reaction (PCR) based techniques that have strongly backed up its predecessor, the far less informative classical serological typing. By applying these modern technologies, we gain the deepest insight into HLA allelic specificities and thus the possibility to, for example, trace and recruit unrelated histocompatible donors for a given patient. In the case when exclusively related intrafamilial HSC donors are being considered, we are confined to the fact that only 25-30% of patients can expect a completely HLA identical donor to be found within core or extended family members. The number of related as well as unrelated donors can be increased if certain HLA mismatches are accepted. When doing so, the precise definition of disparate histocompatibilty antigens between the patient and a possible donor should be carried out. But this does not give us the information about the functional immunogenicity of such differences. Therefore, in vitro functional assays, quantitating the alloreactive potential of lymphocyte T subsets, the central immunocompetent cells, are more than necessary. By evaluating mixed lymphocyte reaction (MLR), the analysis of helper T cell precursor (HTLp) and cytotoxic T cell precursor (CTLp) frequencies, the allogeneic impact of class II and class I HLA mismatches between a donor and graft recipient can be assessed and permissive disparities defined.