Faculty Collaboration Database

Adoptively transferred gamma delta T cells indirectly regulate murine graft-versus-host reactivity following donor leukocyte infusion therapy in mice. J Immunol 2000 Aug 01;165(3):1634-40

Date

07/21/2000

Pubmed ID

10903774

DOI

10.4049/jimmunol.165.3.1634

Scopus ID

2-s2.0-0034254303 (requires institutional sign-in at Scopus site)   36 Citations

Abstract

The purpose of this study was to determine whether gamma delta T cells were able to regulate graft-vs-host (GVH) reactivity mediated by alpha beta T cells in murine recipients transplanted with MHC-mismatched marrow grafts. Studies were conducted using ex vivo-activated gamma delta T cells because this was a more clinically relevant strategy, and these cells have been shown to be capable of facilitating alloengraftment without causing GVH disease (GVHD). Coadministration of activated gamma delta T cells and naive alpha beta T cells at the time of bone marrow transplantation (BMT) significantly exacerbated GVHD when compared with naive alpha beta T cells alone. In contrast, when the administration of naive alpha beta T cells was delayed for 2 wk post-BMT, survival was significantly enhanced in mice transplanted with BM plus activated gamma delta T cells vs those given marrow cells alone. Mitigation of GVHD by activated gamma delta T cells occurred only at high doses (150 x 106) and was a unique property of gamma delta T cells, as activated alpha beta T cells were incapable of ameliorating the subsequent development of GVHD. Protection from GVHD was not due to the direct inhibition of naive alpha beta T cells by gamma delta T cells. Rather, gamma delta T cells mediated this effect indirectly through donor BM-derived alpha beta T cells that acted as the proximate regulatory population responsible for the decrease in GVH reactivity. Collectively, these data demonstrate that activated gamma delta T cells are capable of modulating the ability of MHC-incompatible nontolerant alpha beta T cells to cause GVHD after allogeneic BMT.

Author List

Drobyski WR, Vodanovic-Jankovic S, Klein J

Author

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin

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

Adoptive Transfer
Animals
Bone Marrow Cells
Bone Marrow Transplantation
Dose-Response Relationship, Immunologic
Graft Survival
Graft vs Host Disease
Graft vs Host Reaction
Leukocyte Transfusion
Lymphocyte Activation
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Mice, Knockout
Mice, SCID
Receptors, Antigen, T-Cell, alpha-beta
Receptors, Antigen, T-Cell, gamma-delta
T-Lymphocyte Subsets
Thy-1 Antigens
Thymus Gland