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Different Susceptibilities of Normal T Cells and T Cell Lines to Immunotoxins
Author(s) -
PREIJERS F. W. M. B.,
TAX W. J. M.,
WESSELS J. M. C.,
CAPEL P. J. A.,
WITTE T.,
HAANEN C.
Publication year - 1988
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1988.tb02380.x
Subject(s) - cytotoxic t cell , jurkat cells , microbiology and biotechnology , cytotoxicity , t cell , antigen , immunotoxin , cell culture , clonogenic assay , chemistry , cd5 , biology , immunology , in vitro , flow cytometry , biochemistry , immune system , genetics
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 NH 4 Cl. Treatment of T cells with a cocktail of IT (10 −8 m ) and 20 m m NH 4 Cl 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 m m ammonium chloride.