Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation

Abstract

T cell depletion using the murine monoclonal antibody (moAb) T₁₀B₉ is unique in that the T cell receptor (TCR)γδbearing subset is relatively spared compared to the TCRαβ⁺ subset. We evaluated the probabilities of engraftment, acute and chronic graft-versus-host disease (GVHD), relapse, and survival in 273 recipients of marrow T cell depleted using T₁₀B₉. Sixty-two patients received marrow from an HLA-identical sibling, 54 patients received partially matched related donor marrow and 157 patients received unrelated donor marrow. Limiting dilution analysis (LDA) was used to estimate total clonable T cell dose in all patients and a modified LDA using moAb-coated immunomagnetic beads was used to estimate TCRαβ⁺, CD4⁺ and CD8⁺ T cells in a subset of patients. TCRγδ⁺ cell dose was estimated by flow cytometry. Cox proportional hazards regression models were used to assess the impact of T cell subset dose/kg of body weight on outcome. We found a significant association of TCRγδ⁺ T cell dose (P = 0.004), but not TCRαβ⁺ T cell dose or total clonable T cell dose, with the probability of engraftment. TCRαβ⁺, CD4⁺, CD8⁺ and total clonable T cell dose were significantly associated (P < 0.001) with the risks of grade 2–4 acute gvhd in recipients of marrow from related donors but not in recipients of marrow from unrelated donors. neither total clonable t cell dose nor any t cell subset dose was found to be significantly associated with chronic gvhd, relapse or survival. the results confirm preclinical studies showing tcrγδ⁺ T cells promote engraftment. TCRγδ⁺ T cells are not associated with an increased risk of acute GVHD while TCRαβT cells are associated with acute GVHD but not engraftment in recipients of marrow grafts T cell depleted using T₁₀B₉. These findings support the hypothesis that T cell subsets differentially contribute to alloengraftment and GVHD.