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

Y. Kawanishi, J. Passweg, W. R. Drobyski, P. Rowlings, A. Cook-Craig, J. Casper, D. Pietryga, F. Garbrecht, B. Camitta, M. Horowitz, M. Juckett, D. Margolis, N. Flomenberg, C. A. Keever-Taylor

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


T cell depletion using the murine monoclonal antibody (moAb) T10B9 is unique in that the T cell receptor (TCR)γδ bearing 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 = 0.003), 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 TCRαβ T 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.

Original languageEnglish (US)
Pages (from-to)1069-1077
Number of pages9
JournalBone marrow transplantation
Issue number11
StatePublished - Jun 1 1997
Externally publishedYes

Bibliographical note

Funding Information:
We would like to acknowledge the bone marrow processing laboratory personnel for technical assistance in performing the limiting dilution assays and Dr Susan Koethe and the technical members of the Diagnostic Immunology Laboratory for performance of the flow cytometry assessments. This work was supported in part by an award from the Falk Foundation administered through the Cancer Center of the Medical College of Wisconsin and by the Midwest Athletes against Childhood Cancer (MACC) fund.


  • Bone marrow transplant
  • Graft-versus-host disease
  • Limiting dilution assay
  • T cell depletion
  • TCRαβ T cells
  • TCRγδ T cells


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