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- Title
Different Susceptibilities of Normal T Cells and T Cell Lines to Immunotoxins.
- Authors
Preijers, F. W. M. B.; Tax, W. J. M.; Wessels, J. M. C.; Capel, P. J. A.; de Witte, T.; Haanen, C.
- 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 the monoclonal antibodies (MoAb) WT32 (CD3). T101 (CD5), and WT1 (CD7) to ricin A chain was evaluated. The cytotoxicity of IT was based on protein synthesis inhibition in human T cell lines: CH1, 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 be rather insensitive to IT not due to a low antigen density or decreased internalization. The cytotoxicity of IT to T cells could be enhanced considerably by NH4Cl. Treatment of T cells with a cocktail of IT (10-8 M) 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 phytohaemagglutinin (PHA) prior to incubation with IT considerably increased the sensitivity to IT treatment. Thus, normal I 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 11 to normal 1 cells can be achieved in the presence of 20 mM ammonium chloride.
- Subjects
T cells; BONE marrow; ANTIBODY-toxin conjugates; MONOCLONAL antibodies; PROTEIN synthesis; CELL lines
- Publication
Scandinavian Journal of Immunology, 1988, Vol 27, Issue 5, p533
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1111/j.1365-3083.1988.tb02380.x