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.

T CELLS FROM PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA (PNH) PATIENTS SHOW AN ALTERED CD40-DEPENDENT PATHWAY / Terrazzano, G.; Sica, M; Becchimanzi, C.; Costantini, S.; Rotoli, B.; Zappacosta, S.; Alfinito, Fiorella; Ruggiero, Giuseppina. - In: JOURNAL OF LEUKOCYTE BIOLOGY. - ISSN 0741-5400. - STAMPA. - 78:1(2005), pp. 27-36.

T CELLS FROM PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA (PNH) PATIENTS SHOW AN ALTERED CD40-DEPENDENT PATHWAY

ALFINITO, FIORELLA;RUGGIERO, GIUSEPPINA
2005

Abstract

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.
2005
T CELLS FROM PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA (PNH) PATIENTS SHOW AN ALTERED CD40-DEPENDENT PATHWAY / Terrazzano, G.; Sica, M; Becchimanzi, C.; Costantini, S.; Rotoli, B.; Zappacosta, S.; Alfinito, Fiorella; Ruggiero, Giuseppina. - In: JOURNAL OF LEUKOCYTE BIOLOGY. - ISSN 0741-5400. - STAMPA. - 78:1(2005), pp. 27-36.
File in questo prodotto:
File Dimensione Formato  
Terrazzano et al 05.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: Accesso privato/ristretto
Dimensione 509.99 kB
Formato Adobe PDF
509.99 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/204151
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 16
  • ???jsp.display-item.citation.isi??? ND
social impact