Faculty Collaboration Database

Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation. Bone Marrow Transplant 1997 Jun;19(11):1069-77

Date

06/01/1997

Pubmed ID

9193748

DOI

10.1038/sj.bmt.1700807

Scopus ID

2-s2.0-0030982179 (requires institutional sign-in at Scopus site)   51 Citations

Abstract

T cell depletion using the murine monoclonal antibody (moAb) T10B9 is unique in that the T cell receptor (TCR)gamma delta bearing subset is relatively spared compared to the TCR alpha beta + 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 TCR alpha beta +, CD4+, and CD8+ T cells in a subset of patients. TCR gamma delta + 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 TCR gamma delta + T cell dose (P = 0.004), but not TCR alpha beta + T cell dose or total clonable T cell dose, with the probability of engraftment. TCR alpha beta +, 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 TCR gamma delta + T cells promote engraftment. TCR gamma delta + T cells are not associated with an increased risk of acute GVHD while TCR alpha beta 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.

Author List

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

Authors

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
David A. Margolis MD Interim Chair, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Bone Marrow Transplantation
Child
Child, Preschool
Graft vs Host Disease
Humans
Infant
Lymphocyte Depletion
Middle Aged
Multivariate Analysis
Receptors, Antigen, T-Cell, alpha-beta
Receptors, Antigen, T-Cell, gamma-delta
T-Lymphocyte Subsets