PeproTech Inc.
Originally published online as doi:10.1189/jlb.0105026 on April 7, 2005

Published online before print April 7, 2005
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0105026v1
78/1/27    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Terrazzano, G.
Right arrow Articles by Ruggiero, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Terrazzano, G.
Right arrow Articles by Ruggiero, G.
(Journal of Leukocyte Biology. 2005;78:27-36.)
© 2005 by Society for Leukocyte Biology

T cells from paroxysmal nocturnal haemoglobinuria (PNH) patients show an altered CD40-dependent pathway

Giuseppe Terrazzano*, Michela Sica*, Cristina Becchimanzi{dagger}, Silvia Costantini{dagger}, Bruno Rotoli{dagger}, Serafino Zappacosta*, Fiorella Alfinito{dagger} and Giuseppina Ruggiero*,1

* Cattedra di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, and
{dagger} Cattedra di Ematologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Napoli "Federico II," Naples, Italy

1 Correspondence: Cattedra di Immunologia-Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli "Federico II", Via Pansini 5, 80131 Naples, Italy. E-mail: giruggie{at}unina.it

Paroxysmal nocturnal haemoglobinuria (PNH) is a haematopoiesis disorder characterized by the expansion of a stem cell bearing a somatic mutation in the phosphatidylinositol glycan-A (PIG-A) gene, which is involved in the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor. A number of data suggest the inability of the PIG-A mutation to account alone for the clonal dominance of the GPI-defective clone and for the development of PNH. In this context, additional immune-mediated mechanisms have been hypothesized. We focused on the analysis of T lymphocytes in three PNH patients bearing a mixed GPI+ and GPI– T cell population and showing a marked cytopenia. To analyze the biological mechanisms underlying the control of T cell homeostasis in PNH, we addressed the study of CD40-dependent pathways, suggested to be of crucial relevance for the control of autoreactive T cell clones. Our data revealed significant, functional alterations in GPI+ and GPI– T cell compartments. In the GPI– T cells, severe defects in T cell receptor-dependent proliferation, interferon-{gamma} production, CD25, CD54, and human leukocyte antigen-DR surface expression were observed. By contrast, GPI+ T lymphocytes showed a significant increase of all these parameters, and the analysis of CD40-dependent pathways revealed a functional persistence of CD154 expression on the CD48+CD4+ lymphocytes. The alterations of the GPI+ T cell subset could be involved in the biological mechanisms underlying PNH pathogenesis.

Key Words: GPI-defective clones • cytopenia • immune response