title: 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)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.
authors.affiliation: Bone Marrow Transplantation Program of the Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawanishi
authors.forename: J
authors.initials: J
authors.lastname: Passweg
authors.forename: W R
authors.initials: WR
authors.lastname: Drobyski
authors.forename: P
authors.initials: P
authors.lastname: Rowlings
authors.forename: A
authors.initials: A
authors.lastname: Cook-Craig
authors.forename: J
authors.initials: J
authors.lastname: Casper
authors.forename: D
authors.initials: D
authors.lastname: Pietryga
authors.forename: F
authors.initials: F
authors.lastname: Garbrecht
authors.forename: B
authors.initials: B
authors.lastname: Camitta
authors.forename: M
authors.initials: M
authors.lastname: Horowitz
authors.forename: M
authors.initials: M
authors.lastname: Juckett
authors.forename: D
authors.initials: D
authors.lastname: Margolis
authors.forename: N
authors.initials: N
authors.lastname: Flomenberg
authors.forename: C A
authors.initials: CA
authors.lastname: Keever-Taylor
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008875:Middle Aged; D015999:Multivariate Analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta