A Study on Graft-versus-Host Reaction (GVHR) by Simonsen's Splenomegaly Assay Cells and Antigen Systems Involved in Induction of GVHR

Cells and histocompatibility antigen systems involved in graft-versus-host reactions (GVHR) were analyzed using Simonsen's splenomegaly assay employing various combinations of donor and F₁ hybrid recipients mice. Most of the cells proliferating in spleens of mice undergoing GVHR were J11d⁺, and had histological features of cells of the hematopoietic lineage. The proportions of CD3⁺ T cells were decreased in the spleens. Disparity at minor histocompatibility determinants of AKR, I-E and H-2D regions between B10.A(4R) donors and (4R × AKR) F₁ recipients evoked only negligible GVHR. On the contrary, disparity at H-2K and/or I-A regions appeared to be sufficient to permit induction of full GVHR. When surface markers of donor spleen cells were analyzed, it was shown that Thy-1⁺ and/or MEL-14⁺ cells caused a strong effect on GVHR. Further, either CD4⁺ or CD8⁺ T cell subset could induce significant GVHR. However, synergistic influences of these two T cell subsets on one another in GVHR were observed. The present results raise the possibility of using Simonsen's assay along with a number of reagents to identify the contribution of subsets of T lymphocytes and in analyzing precise contributions of cellular components from both donor and recipient, and also of the target antigen systems of the recipient that contribute to early events involved in GVHR.