A ricin A chain-containing immunotoxin that kills human T lymphocytes in vitro

P. J. Martin, J. A. Hansen, E. S. Vitetta

Research output: Contribution to journalArticle

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Abstract

An immunotoxin specific for human T lymphocytes was prepared by coupling an IgG(2a) anti-CD3 murine monoclonal antibody (64.1) to purified ricin A chain (64.1-A). Treatment of blood mononuclear cells with this immunotoxin at a concentration of 1.7 x 10-9 mol/L for two hours at 37° C in the presence of 20 mmol/L NH4Cl decreased phytohemagglutinin-stimulated protein synthesis by 95%. In addition, a sensitive culture assay showed that fewer than 0.03% T cells remained after treatment of human bone marrow mononuclear cells with 64.1-A at a concentration of 1.7 x 10-9 mol/L. The inhibition of protein synthesis could be prevented by preincubating cells with unconjugated 64.1 antibody but not by preincubating cells with a control IgG(2a) antibody that binds to a different T cell antigen (CD5). At concentrations up to 1 x 10-8 mol/L, 64.1-A had little effect on blood mononuclear cells from baboons or human myeloid precursors (CFU-GM), which do not express the CD3 antigen recognized by 64.1. Taken together, these results indicate that the toxicity of 64.1-A was specific and the 64.1-A may be a useful reagent for depleting T cells from donor marrow as a means of preventing acute graft-v-host disease after allogeneic bone marrow transplantation.

Original languageEnglish (US)
Pages (from-to)908-912
Number of pages5
JournalBlood
Volume66
Issue number4
StatePublished - 1985

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Ricin
Immunotoxins
T-cells
T-Lymphocytes
Blood Cells
Bone
CD5 Antigens
Blood
Immunoglobulin G
CD3 Antigens
Transplantation (surgical)
Granulocyte-Macrophage Progenitor Cells
Antibodies
Papio
Viral Tumor Antigens
Homologous Transplantation
Phytohemagglutinins
Bone Marrow Transplantation
Cell culture
Grafts

ASJC Scopus subject areas

  • Hematology

Cite this

A ricin A chain-containing immunotoxin that kills human T lymphocytes in vitro. / Martin, P. J.; Hansen, J. A.; Vitetta, E. S.

In: Blood, Vol. 66, No. 4, 1985, p. 908-912.

Research output: Contribution to journalArticle

Martin, P. J. ; Hansen, J. A. ; Vitetta, E. S. / A ricin A chain-containing immunotoxin that kills human T lymphocytes in vitro. In: Blood. 1985 ; Vol. 66, No. 4. pp. 908-912.
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