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Anti-tetanus toxoid antibody production after mismatched T cell-depleted bone marrow transplantation

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Abstract

We explored B-cell function after tetanus toxoid (TT) immunization in 12 children with severe combined immunodeficiency disease or leukemia who were long-term survivors of an HLA-matched sibling or haplocompatible T cell-depleted parental bone marrow transplant (BMT), 10 of their healthy donors, and 13 normal controls. Specificin vivo andin vitro anti-TT antibody (Ab) production were measured by ELISA. We studied donors' and recipients' peripheral blood mononuclear cells (PBMC) and mixed E− (non-T cells) and E+ cells (T cells) spontaneously and after stimulation by TT in the absence or presence of interleukin-2 (IL-2), IL-4, and IL-6. Five of the 12 patients and all donors and controls responded within vivo anti-TT Ab.In vitro anti-TT Ab production correlated with thein vivo response. All seven of the nonresponders were either fully engrafted or mixed chimeras (donor T cells but autologous B cells and monocytes). We could not identify a T-cell defect in four of the five nonresponders who were tested. In contrast, E− cells from three of three responders cooperated with fresh donor E+ cells even when they shared only one HLA haplotype. In three of seven nonresponders,in vitro anti-TT Ab production was restored after the addition of IL-4 or IL-6 but not IL-2. Our results suggest that the humoral immunodeficiency that exists post mismatched T cell-depleted BMT is either a B-cell, a monocyte, or a B-cell/T-cell cooperation defect which, in some patients, may be correctible with the addition of a cytokine. Also, it is not necessary to engraft donor B cells to achieve normal antibody responses and the ability to respond does not appear to correlate with pretransplant chemotherapy.

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Authors and Affiliations

  1. Division of Bone Marrow Transplantation, Department of Pediatrics, University of California, 94143-1278, San Francisco, California

    Y. Dror, A. Merino & M. J. Cowan

  2. Division of Immunology, Department of Pediatrics, University of California, 94143, San Francisco, California

    M. Benkerrou, D. W. Wara & M. Elder

  3. Division of Immunogenetics and Transplantation, Department of Surgery, University of California, 94143, San Francisco, California

    B. W. Colombe & M. Garovoy

Authors
  1. M. Benkerrou
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  2. D. W. Wara
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  3. M. Elder
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  4. Y. Dror
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  5. A. Merino
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  6. B. W. Colombe
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  7. M. Garovoy
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  8. M. J. Cowan
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Benkerrou, M., Wara, D.W., Elder, M. et al. Anti-tetanus toxoid antibody production after mismatched T cell-depleted bone marrow transplantation. J Clin Immunol 14, 98–106 (1994). https://doi.org/10.1007/BF01541342

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  • DOI: https://doi.org/10.1007/BF01541342

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