T cell repertoire complexity is conserved after LLME treatment of donor lymphocyte infusions.
Publication/Presentation Date
12-1-2007
Abstract
Slow reconstitution of the T cell repertoire after allogeneic blood or bone marrow stem cell transplantation is a major risk factor for patient mortality. The delivery of immunocompetent T cells as delayed donor lymphocyte infusions (DLIs) is a potential way of counteracting this problem. The development of graft-versus-host disease (GVHD) is a potential complication of this procedure, however. We previously found that in P-->F1 haploidentical murine models, the ex-vivo treatment of donor lymphocytes with L-leucyl-L-leucine methyl ester (LLME) can prevent the onset of GVHD after DLI, likely by inducing cell death in most of the perforin-positive CD8(+) T cells and in a fraction of CD4(+) T cells. Our previous preclinical studies have formed the basis of an ongoing phase I clinical trial in which patients received LLME-treated DLI from their original donor in an attempt to accelerate T cell reconstitution. To understand how this treatment strategy might affect the complexity of the DLI T cell repertoire, we used T cell receptor Vbeta spectratype analysis to evaluate the DLI product pre-LLME and post-LLME treatment. The results indicated that the LLME-treated DLI product exhibited CDR3-size distribution complexities similar to those of its untreated donor sample. In addition, comparisons of the CD4(+) and CD8(+) T cell repertoire from the donor before LLME treatment with that of the recipient post-DLI demonstrated equal complexity for most of the resolvable Vbeta families. Finally, the in vitro proliferative capacity of LLME-treated DLI product in response to allo-stimulation in a one-way mixed lymphocyte reaction was comparable to that of the untreated product.
Volume
13
Issue
12
First Page
1439
Last Page
1447
ISSN
1083-8791
Published In/Presented At
Friedman, T. M., Filicko-O'Hara, J., Mookerjee, B., Wagner, J. L., Grosso, D. A., Flomenberg, N., & Korngold, R. (2007). T cell repertoire complexity is conserved after LLME treatment of donor lymphocyte infusions. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 13(12), 1439–1447. https://doi.org/10.1016/j.bbmt.2007.09.008
Disciplines
Medicine and Health Sciences
PubMedID
18022573
Department(s)
Hematology-Medical Oncology Division
Document Type
Article