Recombinant anti-monkey CD3 immunotoxin depletes peripheral lymph node T lymphocytes more effectively than rabbit anti-thymocyte globulin in naive baboons

    Authors

    I. Wamala; A. J. Matar; E. Farkash; Z. R. Wang; C. A. Huang;D. H. Sachs

    Comments

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    Abbreviated Journal Title

    Transpl. Immunol.

    Keywords

    T-cell; ATG; Immunotoxin; Depletion; Lymph node; RENAL-ALLOGRAFT SURVIVAL; TOXIN-BASED IMMUNOTOXIN; CELL DEPLETION; MONOCLONAL-ANTIBODY; INDUCTION THERAPY; KIDNEY ALLOGRAFT; MIXED; CHIMERISM; RHESUS-MONKEYS; BONE-MARROW; TOLERANCE; Immunology; Transplantation

    Abstract

    T cell depletion is an important procedure for both experimental and therapeutic immune modulation. Rabbit anti-thymocyte globulin (ATG), which is a commonly used T cell depletion antibody in clinical organ and cell transplantation protocols, is effective in temporarily depleting peripheral blood T lymphocytes but only moderately effective in depleting peripheral lymph node T cells which comprise the majority of T lymphocytes. A recombinant anti-CD3 immunotoxin, A-dmDT390-scfbDb (007), has been developed and shown in an initial study to retain the lymph node depleting properties of conjugated CD3 immunotoxin. This agent could potentially be used synergistically with or as a replacement for rabbit ATG in preclinical primate models of transplantation. We directly compared the peripheral blood and lymph node depleting abilities of this recombinant anti-CD3 immunotoxin and rabbit ATG in naive animals at clinically tolerated doses. Baboons were treated with a full course of either rabbit ATG (n = 2) or CD3 immunotoxin (n = 3). Peripheral blood and lymph node T lymphocytes were measured before and following treatment. Peripheral blood CD3 + cells fell below 100 cells/mu L in every animal. In the two animals receiving ATG, CD3 + cells represented 53% and 68% of lymph node cells two days following a full course of rabbit ATG. In contrast, CD3 + cells represented 3%, 5%, and 38% in lymph nodes following a full course of CD3-IT. Thus, recombinant anti-monkey CD3 immunotoxin showed improved peripheral lymph node T lymphocyte depletion to rabbit ATG and spared other immune cells. (C) 2013 Published by Elsevier B.V.

    Journal Title

    Transplant Immunology

    Volume

    29

    Issue/Number

    1-4

    Publication Date

    1-1-2013

    Document Type

    Article

    Language

    English

    First Page

    60

    Last Page

    63

    WOS Identifier

    WOS:000329145600011

    ISSN

    0966-3274

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