Generation of leukemia-reactive cytotoxic T lymphocytes from HLA-identical donors of patients with chronic myeloid leukemia using modifications of a limiting dilution assay

Bone Marrow Transplantation
W M SmitJ H Falkenburg

Abstract

Donor leukocyte transfusions (DLT) have an anti-leukemic effect in most patients with a relapse of chronic myeloid leukemia (CML) after allogeneic stem cell transplantation. However, DLT are often complicated by graft-versus-host disease. Selection of donor lymphocytes with a relative specificity for leukemic cells is desirable. The generation of leukemia-reactive cytotoxic T lymphocyte (CTL) responses between HLA-identical donors and patients in bulk cultures showed major variations, and false negative results were observed. In a modification of a limiting dilution analysis (LDA) two-fold serial dilutions of HLA-identical donor mononuclear cells (MNC) were cultured in the presence of CML cells. The anti-leukemic CTL precursor frequencies in these donors varied between <1 and 9 per 106 MNC. HLA-restricted CD4+ or CD8+ lymphocytes as well as MHC non-restricted gammadelta T cells were responsible for the anti-leukemic responses. A positive correlation between cytotoxicity in the various wells after 3, 4 and 5 weeks of culture could be found. The LDA may be superior to bulk cultures in selecting stable immune responses and in separating multiple different anti-leukemic T cell responses in each donor-patient combination.

Citations

Jul 5, 2003·Experimental Hematology·Imad A Tabbara, Richard M Ingram
Sep 6, 2003·Methods : a Companion to Methods in Enzymology·M A W G van der HoornJ H F Falkenburg
Jul 11, 2000·British Journal of Haematology·L C NorburyS E Christmas
Aug 28, 2001·Journal of Hematotherapy & Stem Cell Research·W A Marijt, J H Falkenburg
Jul 10, 1999·Current Opinion in Hematology·U R Osarogiagbon, P B McGlave
Jun 22, 1999·Lancet·J J MelenhorstJ H Falkenburg
Nov 8, 2001·Leukemia & Lymphoma·R E Clark, S E Christmas
Nov 4, 2000·Expert Opinion on Investigational Drugs·P Maslak, D Scheinberg
Apr 2, 2002·Best Practice & Research. Clinical Haematology·M Battiwalla, J Barrett
Feb 6, 2004·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·F A CastroJ C Voltarelli
Jul 4, 2001·Bone Marrow Transplantation·R ChamplinS Giralt
Apr 5, 2005·The International Journal of Neuroscience·Zhi ZhuangShangkai Gao
Jan 24, 2006·American Journal of Veterinary Research·Sofie F BhattiHans S Kooistra
Feb 25, 2009·Clinical and Experimental Medicine·Michela Cesco-GaspereHans J Stauss
May 25, 2011·International Journal of Pediatric Obesity : IJPO : an Official Journal of the International Association for the Study of Obesity·Katharina DiethelmAnette E Buyken
Jul 29, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Luciana BesedovskyTanja Lange
Oct 22, 2002·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Ferenc ObalJames M Krueger
Mar 8, 2002·American Journal of Physiology. Endocrinology and Metabolism·Hiralal G MaheshwariGerhard Baumann
Nov 28, 2001·Hematology·R F StorbE H Warren
Feb 20, 2007·Hormone Research·Eve Van CauterKarine Spiegel
Mar 31, 2011·American Journal of Physiology. Endocrinology and Metabolism·Claire E H M DonjacourHanno Pijl
Jul 25, 2007·Cephalalgia : an International Journal of Headache·E L MeyerE Waldenlind
Dec 18, 2001·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·I HajduC D Rollo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.