Selective elimination in vitro of alloresponsive T cells to human transplantation antigens by toxin or radionuclide conjugated anti-IL-2 receptor (Tac) monoclonal antibody

Journal Article · Tue May 01 04:00:00 EDT 1990 · Journal of Immunology; (USA)

OSTI ID:7045524

Kozak, R W; Fitzgerald, D P; Atcher, R W; Goldman, C K; Nelson, D L; Gansow, O A; Pastan, I; Waldmann, T A ^[1]

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1. Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (USA)

The human allogeneic mixed lymphocyte reaction is the in vitro correlate of graft rejection. Cytotoxic effector cells generated during an allogeneic mixed lymphocyte reaction were previously shown to express the human p55 IL-2 receptor subunit, whereas resting cells do not express this receptor peptide. In this study, we asked whether Pseudomonas exotoxin or bismuth-212 (an alpha-particle emitting radionuclide) coupled to the anti-IL-2 receptor mAb, anti-Tac, were able to selectively eliminate alloresponsive cells generated during an allogeneic mixed lymphocyte reaction. After assembly, anti-Tac immunoconjugates retained their binding integrity, specificity, and selectivity. Deletion of alloresponsive cells was shown by the removal of alloproliferating cells as assessed by quantitating cell recovery and by measurement of thymidine incorporation into newly synthesized DNA. Both toxin and radionuclide immunoconjugates eliminated established cytotoxic effector cells generated in an allogeneic mixed lymphocyte reaction, while leaving intact the PHA-inducible mitogenic response of the nonactivated cells. The addition of excess anti-Tac blocked all of the effects of these cytotoxic reagents. The therapeutic reagents in vitro were most effective when added just prior to the peak of the alloproliferative response, when receptor expression would be close to maximum. Thus, anti-Tac conjugated either with toxin or radionuclide is effective in vitro in specifically eliminating cytotoxic effector cells.

• OSTI ID: 7045524
• Journal Information: Journal of Immunology; (USA), Journal Name: Journal of Immunology; (USA) Vol. 144:9; ISSN 0022-1767; ISSN JOIMA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALPHA DECAY RADIOISOTOPES
ANIMAL CELLS
ANIMALS
ANTIBODIES
ANTIBODY FORMATION
ANTIGENS
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BISMUTH 212
BISMUTH ISOTOPES
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
GROWTH FACTORS
HEAVY NUCLEI
HOURS LIVING RADIOISOTOPES
IN VITRO
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MICROORGANISMS
MITOGENS
MONOCLONAL ANTIBODIES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
PSEUDOMONAS
RADIOISOTOPES
REACTION KINETICS
REAGENTS
RECEPTORS
SOMATIC CELLS
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
VERTEBRATES