Detection of HLA restricted anti-minor histocompatibility antigen(s) reactive cells from skin GVHD lesions.

Recipients of marrow grafts from HLA-identical, (including MLC non-reactive) sibling donors have a 40-50% incidence of acute graft vs. host disease (GVHD); the involvement of non-HLA linked, minor histocompatibility antigens (miHA) has been implicated. One of the target tissues of GVHD is the skin where morphological analysis of biopsy specimens is often used to support this diagnosis. We have obtained skin biopsy specimens from the site of GVHD lesions, grown the cells in the presence of T cell growth factor (TCGF) and feeder cells, and tested these cultured cells in the primed lymphocyte test (PLT) and cell mediated lympholysis (CML) assay. Five of six cell cultures tested demonstrated secondary proliferative but not cytolytic reactivity; cells from one culture demonstrated both reactivities. The cell culture populations generated are presumably directed against non-HLA antigens, i.e., miHA whose expression is restricted by an HLA antigen of the recipient. The data are consistent with the suggestion that in the majority of these cultures, the restriction element may be a determinant encoded within the HLA-D region: DQ, DR, and possibly DP based on panel testing. Although the number of cases is small, these preliminary data demonstrate the feasibility of this type of culturing system and also suggest that the cellular immunological events leading to the manifestation of skin GVHD lesions may be predominantly a delayed type hypersensitivity reaction.