PNH cells are as sensitive to T-cell-mediated lysis as their normal counterparts: Implications for the pathogenesis of paroxysmal nocturnal haemoglobinuria Journal Article

  


Authors: Karadimitris, A.; Notaro, R.; Koehne, G.; Roberts, I. A. G.; Luzzatto, L.
Article Title: PNH cells are as sensitive to T-cell-mediated lysis as their normal counterparts: Implications for the pathogenesis of paroxysmal nocturnal haemoglobinuria
Abstract: The mechanism responsible for the bone marrow failure that is almost invariable in paroxysmal nocturnal haemoglobinuria (PNH) is unknown. Based on the close association between PNH and idiopathic aplastic anaemia, a plausible pathogenetic model predicts that, in PNH, autoreactive T cells specific for haemopoietic stem cells (HSCs) cause depletion of normal HSCs, whereas PNH HSCs escape this T-cell-mediated attack. In this study, we addressed the hypothesis that PNH HSCs are resistant to the cytotoxic effect of T cells because they lack surface expression of one or more glycosylphosphatidylinositol (GPI)-linked molecules. We tested the sensitivity of normal and PNH Epstein - Barr virus (EBV)-transformed B-cell lymphoblastoid cell lines (BLCLs) to the cytotoxic effect of autologous EBV-specific T-cell lines and clones from a patient with PNH in an in vitro experimental system. We found that the PNH BLCLs were no less sensitive to T-cell-mediated cytotoxicity than non-PNH isogenic BLCLs, indicating that GPI-linked molecules on the surface of target cells are not required for killing by T cells. This suggests that the mechanism whereby PNH HSCs survive T-cell attack is not because of the lack of surface expression of one or more GPI-linked molecules. By implication, other mechanisms become more probable.
Keywords: controlled study; human cell; pathogenesis; t cells; t lymphocyte; cell death; cell survival; cytotoxicity; lymphoma, b-cell; t-lymphocytes, cytotoxic; cell line, transformed; stem cells; cytolysis; cytotoxicity, immunologic; hematopoietic stem cell; epstein barr virus; herpesvirus 4, human; paroxysmal nocturnal hemoglobinuria; hemoglobinuria, paroxysmal; coculture techniques; glycosylphosphatidylinositol; pnh; antigens, cd59; humans; human; priority journal; article; pnh and non-pnh targets
Journal Title: British Journal of Haematology
Volume: 111
Issue: 4
ISSN: 0007-1048
Publisher: John Wiley & Sons  
Date Published: 2000-12-01
Start Page: 1158
End Page: 1163
Language: English
DOI: 10.1111/j.1365-2141.2000.02494.x
PUBMED: 11167756
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0034489990&partnerID=40&md5=8badb31a28b1a22617c914d0869ff7a3
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Rosario Notaro
    22 Notaro
  2. Anastasios Karadimitris
    13 Karadimitris
  3. Guenther Koehne
    194 Koehne
  4. Lucio Luzzatto
    105 Luzzatto
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