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T cells from paroxysmal nocturnal haemoglobinuria (PNH) patients show an altered CD40‐dependent pathway
Author(s) -
Terrazzano Giuseppe,
Sica Michela,
Becchimanzi Cristina,
Costantini Silvia,
Rotoli Bruno,
Zappacosta Serafino,
Alfinito Fiorella,
Ruggiero Giuseppina
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0105026
Subject(s) - biology , nocturnal , immunology , medicine , microbiology and biotechnology , endocrinology , ecology
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‐γ 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.