Patient HLA-DP-specific CD4+ T Cells from HLA-DPB1-mismatched Donor Lymphocyte Infusion Can Induce Graft-versus-leukemia Reactivity in the Presence or Absence of Graft-versus-host Disease
Overview
Authors
Affiliations
Clinical studies have demonstrated that HLA-DPB1-mismatched allogeneic stem cell transplantation (allo-SCT) is associated with a decreased risk of disease relapse and an increased risk of graft-versus-host disease (GVHD) compared with HLA-DPB1-matched SCT. In T cell-depleted allo-SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, but a significant decreased risk of disease relapse was still observed. To investigate whether patient HLA-DP-specific CD4(+) T cell responses were frequently induced after T cell-depleted HLA-DPB1-mismatched allo-SCT and donor lymphocyte infusion (DLI), we developed a method to screen for the presence of HLA-DP-specific CD4(+) T cells using CD137 as an activation marker and analyzed 24 patient-donor combinations. The patients suffered from various B cell malignancies, multiple myeloma, and myeloid leukemias. Patient HLA-DP-specific CD4(+) T cells were detected after DLI in 13 of 18 patients who exhibited a clinical response to DLI, compared with only 1 of 6 patients without a clinical response to DLI. Eight patients developed significant GVHD. These data show that patient HLA-DP-specific CD4(+) T cells frequently occur after HLA-DPB1-mismatched T cell-depleted allo-SCT and DLI, and are associated with graft-versus-leukemia reactivity both in the presence and absence of GVHD.
Rambaldi B, Rizzuto G, Rambaldi A, Introna M Front Immunol. 2024; 15:1459175.
PMID: 39512351 PMC: 11540647. DOI: 10.3389/fimmu.2024.1459175.
Katsuyama N, Kawase T, Barakat C, Mizuno S, Tomita A, Ozeki K Nagoya J Med Sci. 2023; 85(4):779-796.
PMID: 38155626 PMC: 10751490. DOI: 10.18999/nagjms.85.4.779.
Barakat C, Inagaki Y, Mizuno S, Nishio N, Katsuyama N, Sato Y Int J Hematol. 2023; 118(2):252-266.
PMID: 37310580 DOI: 10.1007/s12185-023-03621-y.
Laghmouchi A, Kester M, Hoogstraten C, Hageman L, de Klerk W, Huisman W Front Immunol. 2022; 13:831822.
PMID: 35251023 PMC: 8888658. DOI: 10.3389/fimmu.2022.831822.
Revisit of Optimal Donor Number Estimation in the Hong Kong Bone Marrow Donor Registry.
Ho J, Cheung S, Lui Z, Tang I, Yang W, Ip P Front Immunol. 2021; 12:638253.
PMID: 33936051 PMC: 8085527. DOI: 10.3389/fimmu.2021.638253.