Human T Lymphocyte Differentiation Antigens as Target for Immunotoxins or Complement‐Mediated Cytotoxicity

Abstract

Graft‐versus‐host disease (GVHD) after allogeneic hone marrow transplantation (BMT) is initiated by immunocompetent T fells present in the graft. Selective elimination of distinct T‐cell subsets or a sufficient, but not complete T‐cell depletion, might abolish severe GVHD without graft rejection and loss of the anti‐tumour potential. In this study we analysed the efficacy of different monoclonal antibodies (MoAb) WT32(CD3), OKT4(CD4), T101 (CDS), WT1 (CD7), and WT82 (CD8) with respect to their cytotoxicity to T cells cither as immunotoxin (IT) or in combination with complement. The cytotoxic potential was assessed by protein synthesis inhibition and clonogenic a minor effect on blood or bone marrow T cells, although they were highly inhibitory to T‐cell lines. However, in the presence of 20 mm ammonium chloride, IT directed against CD3, CDS, and CD7 were highly cytotoxic. IT directed against CD4 and CD8 were less effective, due to a low internalization. The complement‐mediated cytotoxicity was efficient for all antigens used. The natural killer (NK) activity, as measured by cytotoxicity to K562, was hardly depressed by anti‐CD3, anti‐CD4, anti‐CD5, and anti‐CD8, but was eliminated by ami‐CD7. All procedures used had only a minimal effect on haematopoietic progenitors as measured by CFU‐GM and BFU‐E assays. We concluded that, although the T‐cell population can be eliminated with the combination of anti‐CD3, anti‐CD5, and anti‐CD7 antibodies plus complement, IT with 20 mm NH₄CI appear to kill higher amounts of T cells‐ Selective elimination of CD4‐ and CD8‐positive cells is effectively obtained by MoAb with complement.