Anti-tetanus toxoid antibody production after mismatched T cell-depleted bone marrow transplantation.
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. Specific in vivo and in 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 with in vivo anti-TT Ab. In vitro anti-TT Ab production correlated with the in 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.
Benkerrou
M
M
Department of Pediatrics, University of California, San Francisco 94143-1278.
Wara
D W
DW
Elder
M
M
Dror
Y
Y
Merino
A
A
Colombe
B W
BW
Garovoy
M
M
Cowan
M J
MJ
D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002478:Cells, Cultured; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007223:Infant; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*
D016207:Cytokines; D007074:Immunoglobulin G; D013745:Tetanus Toxoid