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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 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: GH1, CEM, HPB-ALL, and Jurkat, and appeared closely related to the antigen density and internalization rate of 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 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.

journal_name

Scand J Immunol

journal_title

Scandinavian journal of immunology

authors

Preijers FW,Tax WJ,Wessels JM,Capel PJ,De Witte T,Haanen C

doi

10.1111/j.1365-3083.1988.tb02380.x

subject

Has Abstract

pub_date

1988-05-01 00:00:00

pages

533-40

issue

5

eissn

0300-9475

issn

1365-3083

journal_volume

27

pub_type

杂志文章

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