Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders

• Verfasst von: Hofmann, Susanne [VerfasserIn]
• Verfasst von: Schmitt, Michael [VerfasserIn]
• Titel: Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders
• Verf.angabe: Susanne Hofmann, Michael Schmitt, Marlies Götz, Hartmut Döhner, Markus Wiesneth, Donald Bunjes and Jochen Greiner
• Jahr des Originals: 2018
• Umfang: 12 S.
• Fussnoten: Online 14 Jul 2018 ; Gesehen am 15.02.2019
• Titel Quelle: Enthalten in: International journal of cancer
• Jahr Quelle: 2019
• Band/Heft Quelle: 144(2019), 5, S. 1135-1146
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.31753
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1587710277

Abstract

T cell responses against malignant cells play a major role in maintaining remission and prolonging overall survival in patients after allogeneic stem cell transplantation and donor lymphocyte infusion (DLI) due to graft-versus-leukemia effect. For better characterization of the T cell responses, we assessed frequency and diversity of leukemia-associated antigen (LAA)-specific cytotoxic T cells using ELISpot and pMHC multimer assays and analyzed the frequency of regulatory T cells (Treg) as well as cytokine profiles before/after DLI. The data were correlated to the clinical course of patients. Significantly more LAA-derived T cell epitopes (p = 0.02) were recognized in clinical responders (R) when compared to nonresponders (NR). In addition, pMHC multimer-based flow cytometry showed a significantly higher frequency of LAA-specific T cells in R versus NR. The frequency of Treg in R decreased significantly (p = 0.008) while keeping stable in NR. No differences in T cell subset analysis before/after DLI were revealed. Clinical responders were correlated to specific immune responses and all clinical responders showed an increase of specific immune responses after DLI. Cytokine assays using enzyme-linked immunosorbent assay showed a significant increase of IL-4 after DLI. Taken together, an increase of specific CTL responses against several LAA after DLI was detected. Moreover, this study suggests that enhanced LAA diversity in T cell responses as well as decreasing numbers of Treg contribute to clinical outcome of patients treated with DLI.