Different Susceptibilities of Normal T Cells and T Cell Lines to Immunotoxins

Abstract

In the context of ex vivo T cell elimination from bone marrow, the anti‐T cell cytotoxic potential of immunotoxins (IT) prepared by conjugation of die monoclonal antibodies (MOAb) WT32 (CD3), T101 (CD5), and WT1 (CD7) to ricin A chaw was evaluated. The cytotoxicity of IT was based on protein synthesis inhibition in human T cell lines: GHI, CEM, HPB‐ALL, and Jurkat, and appeared closely related to the antigen density and internalization rate of the IT. Normal unstimulated T cells appeared to he rather insensitive to IT not due to a low antigen density or decreased internalization. The cytotoxicity of IT to T cells could he enhanced considerably by NH₄Cl. Treatment of T cells with a cocktail of IT (10⁻⁸m) and 20 mm NH₄Cl resulted in a 5000‐fold cytoreduction as measured by clonogenic assays of limiting T cell dilutions, whereas the haematopoietic progenitor cells remained unaltered. Stimulation of T cells with phytobaemag‐glutinin (PHA) prior to incubation with IT considerably increased the sensitivity to IT treatment. Thus, normal T cells are less sensitive to anti‐T cell IT than T cell lines and activated T cells. This suggests that a low protein synthesis is responsible for the resistance to IT. However, a high specific cytotoxicity of IT to normal T cells can be achieved in the presence of 20 mm ammonium chloride.