Direct cloning of leukemia-reactive T cells from patients treated with donor lymphocyte infusions shows a relative dominance of hematopoiesis-restricted minor histocompatibility antigen HA-1 and HA-2 specific T cells
| Autor: | W. A. F. Marijt, A.M. Barbui, R.A. van Soest, M.P.W. Strijbosch, S.A.P. van Luxemburg-Heijs, Freke M. Kloosterboer, H.M. van Egmond, Els Goulmy, Michel G.D. Kester, Roelof Willemze, J.H.F. Falkenburg |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Cytotoxicity
Immunologic Male Cancer Research T-Lymphocytes T cell Cell Culture Techniques Graft vs Leukemia Effect Biology Minor Histocompatibility Antigens Interleukin 21 Leukemia Myelogenous Chronic BCR-ABL Positive medicine Humans Transplantation Homologous Cytotoxic T cell Antigen-presenting cell Interleukin 3 Salvage Therapy HLA-DR Antigens Hematology T lymphocyte Natural killer T cell Clone Cells Hematopoiesis Neoplasm Proteins medicine.anatomical_structure Oncology Lymphocyte Transfusion Immunology Female Multiple Myeloma Oligopeptides CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Leukemia, 18, 798-808 Leukemia |
| Popis: | Donor T cells recognizing hematopoiesis-restricted minor histocompatibility antigens (mHags) HA-1 and HA-2 on malignant cells play a role in the antileukemia effect of donor lymphocyte infusion (DLI) in patients with relapsed leukemia after allogeneic stem cell transplantation. We quantified the contribution of HA-1 and HA-2 specific T cells to the total number of leukemia-reactive T cells in three HA-2 and/or HA-1 positive patients responding to DLI from their mHag negative donors. Clinical responses occurring 5-7 weeks after DLI were accompanied by an increase in percentages HLA-DR expressing T cells within the CD8+ T cell population. To clonally analyze the leukemia-reactive immune response, T cells responding to the malignancy by secreting IFNgamma were isolated from peripheral blood, directly cloned, and expanded. Tetramer analysis and specific lysis of peptide-pulsed target cells showed that 3-35% of cytotoxic T lymphocyte (CTL) clones isolated were specific for HA-1 or HA-2. TCR VB analysis showed oligoclonal origin of the HA-1 and HA-2 specific CTL clones. The HA-1 and HA-2 specific CTL clones inhibited leukemic progenitor cell growth in vitro. The relatively high frequency of HA-1 and HA-2 specific T cells within the total number of tumor-reactive T cells illustrates relative immunodominance of mHags HA-1 and HA-2. |
| Databáze: | OpenAIRE |
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