Open AccessCytotoxicity against human peripheral blood mononuclear cells and T cell lines mediated by anti‐T cell immunotoxins in the absence of added potentiator
Author(s) -
FISHWILD D. M.,
STASKAWICZ M. O.,
WU H.M.,
CARROLL S. F.
Publication year - 1991
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1991.tb02961.x
Subject(s) - potentiator , cytotoxicity , peripheral blood mononuclear cell , immunotoxin , cytotoxic t cell , monoclonal antibody , in vitro , in vivo , t cell , immunology , cell culture , chemistry , antibody , pharmacology , biology , immune system , biochemistry , genetics , microbiology and biotechnology
SUMMARY Several in vitro assays have indicated that anti‐T cell immunotoxins (IT), composed of monoclonal antibodies (MoAbs)conjugated to ricin A chain (RTA), are maximally effective against T cells only in the presence of potentiators. It was thought that such IT might not be sufficiently cytotoxic to deplete T cells in vivo upon administration to patients. Therefore, we have re‐evaluated the in vitro assays and report herein that even with a short exposure lime (2 h), the two anti‐T cell IT, H65‐RTA (anti‐CD5 MoAb coupled to RTA) and 4MRTA (anti‐CD7 MoAb coupled to RTA 30 ), were specifically cytotoxic for peripheral blood mononuclear cells(PBMC)in the absence of potentiators. Moreover, as has been reported for IT when tested against T cell lines, prolonging the exposure lime of the IT with PBMC from 2 h to as long as 90 h, without added potentiators, enhanced their cytotoxicity from 2‐ to 40‐fold. In contrast, most T cell lines were more sensitive to IT in the presence of potentiator, and IT cytotoxicity was much less enhanced by prolonging the exposure time. Thus, T cell lines may not serve as accurate models to determine the efficacy of IT against PBMC in vitro or in vivo . We conclude that IT‐induced cytotoxicity of PBMC can be demonstrated in vitro at pharmacologically achievable concentrations in the absence of added potentiators.