ANTITETANUS 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 haplocompati ble 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 d onors' and recipients' peripheral blood mononuclear cells (PBMC) and m ixed E- (non-T cells) and E+ cells (T cells) spontaneously and after s timulation by TT in the absence or presence of interleukin-2 (IL-2), I L-4, and IL-6. Five of the 12 patients and all donors and controls res ponded with in vivo anti-TT Ab. In vitro anti-TT Ab production correla ted with the in vivo response. All seven of the nonresponders were eit her 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 th ree 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 immunodefi ciency that exists post mismatched T cell-depleted BMT is either a B-c ell, 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.