Faculty Collaboration Database

Tracking ex vivo-expanded CD4+CD25+ and CD8+CD25+ regulatory T cells after infusion to prevent donor lymphocyte infusion-induced lethal acute graft-versus-host disease. Biol Blood Marrow Transplant 2004 Nov;10(11):748-60

Date

10/27/2004

Pubmed ID

15505606

DOI

10.1016/j.bbmt.2004.07.004

Scopus ID

2-s2.0-6444235650 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

Donor bone marrow (BM)-derived CD4+ CD25+ regulatory T cells, maturing in the host thymus, are critical in inhibiting graft-versus-host disease (GVHD) after donor lymphocyte infusion (DLI) in murine BM chimeras. Data presented here demonstrate that fresh CD25+ cells isolated from donor-type mice can be expanded ex vivo by a variety of methods. Ex vivo-expanded CD4+ CD25+ and CD8+ CD25+ cells were potent suppressors of donor response to host alloantigens in mixed lymphocyte reaction assays. Both fresh and ex vivo-expanded CD4+ CD25+ cells persisted long-term in vivo and effectively prevented DLI-induced GVHD in CD25-/- BM chimeras. Importantly, co-infused CD4+ CD25+ cells with DLI cells migrated to peripheral lymphoid organs and survived long-term in DLI-treated CD25-/- chimeras, but not in DLI-treated CD25+/+ chimeras, indicating homeostatic control of CD25+ cells and an available niche required for their long-term persistence. Furthermore, maintenance of CD25 expression seemed necessary for suppressive function, because only the CD25+ cell fraction, but not the CD25- fraction isolated after adoptive transfer, was suppressive in vitro. Ex vivo-expanded CD8+ CD25+ cells weakly prevented GVHD, apparently because of a rapid disappearance of these cells after adoptive transfer. Taken together, these data suggest that the therapeutic use of ex vivo-expanded CD4+ CD25+ cells may be a feasible, nontoxic modality for controlling GVHD in the clinic. Because of strict homeostatic control, an available niche may be required for long-term persistence of infused regulatory T cells.

Author List

Xia G, Kovochich M, Truitt RL, Johnson BD

Authors

Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Robert L. Truitt PhD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin

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

Animals
Bone Marrow Transplantation
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Graft vs Host Disease
Lymphocyte Transfusion
Mice
Receptors, Interleukin-2