Gamma delta T lymphocytes are thought to play a role in the pathogenesis of multiple sclerosis (MS) contributing to demyelinization and fibrosis in the central nervous system. In this study, we show that, in MS patients with active disease, the percentage of circulating V delta 2+ gamma delta T cells coexpressing NKRP1A is significantly increased compared with healthy donors. V delta 2+ and V delta 1+ T cells were sorted from MS patients and healthy volunteers and cloned. At variance with V delta 1+ clones, all V delta 2+ clones expressed NKRP1A, which was strongly up-regulated upon culture with IL-12; this effect was neutralized by specific anti-IL-12 Abs. No up-regulation of NKRP1A by IL-12 was noted on V delta 1+ clones. RNase protection assay showed that IL-12R beta 2 subunit transcript was significantly less represented in V delta 1+ than V delta 2+ clones. This finding may explain the different effect exerted by IL-12 on these clones. In transendothelial migration assays, V delta 2+ NKRP1A+ clones migrated more effectively than V delta 1+ clones, and this migratory potential was enhanced following culture with IL-12. Migration was strongly inhibited by the F(ab')2 of an anti-NKRP1A Ab, suggesting that this lectin is involved in the migration process. We also show that, in freshly isolated PBMC from MS patients, the migrated population was enriched for V delta 2+ NKRP1A+ cells. We conclude that the expression of NKRP1A on V delta 2+ cells is associated with increased ability to migrate across the vascular endothelium and that this phenomenon may be regulated by IL-12 present in the microenvironment.

Interleukin-12 mediated NKRP1A upregulation and consequent enhancement of endothelial transmigration of Vd2+ TCRgd+ T lymphocytes from healthy donors and multiple sclerosis / Poggi, A; Zocchi, Mr; Costa, P; Ferrero, E; Borsellino, G; Placido, R; Galgani, S; Salvetti, Marco; Gasperini, Claudio; Ristori, Giovanni; BROSNAN CF AND BATTISTINI, L.. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 162:(1999), pp. 4349-4354.

Interleukin-12 mediated NKRP1A upregulation and consequent enhancement of endothelial transmigration of Vd2+ TCRgd+ T lymphocytes from healthy donors and multiple sclerosis

SALVETTI, Marco;GASPERINI, claudio;RISTORI, GIOVANNI;
1999

Abstract

Gamma delta T lymphocytes are thought to play a role in the pathogenesis of multiple sclerosis (MS) contributing to demyelinization and fibrosis in the central nervous system. In this study, we show that, in MS patients with active disease, the percentage of circulating V delta 2+ gamma delta T cells coexpressing NKRP1A is significantly increased compared with healthy donors. V delta 2+ and V delta 1+ T cells were sorted from MS patients and healthy volunteers and cloned. At variance with V delta 1+ clones, all V delta 2+ clones expressed NKRP1A, which was strongly up-regulated upon culture with IL-12; this effect was neutralized by specific anti-IL-12 Abs. No up-regulation of NKRP1A by IL-12 was noted on V delta 1+ clones. RNase protection assay showed that IL-12R beta 2 subunit transcript was significantly less represented in V delta 1+ than V delta 2+ clones. This finding may explain the different effect exerted by IL-12 on these clones. In transendothelial migration assays, V delta 2+ NKRP1A+ clones migrated more effectively than V delta 1+ clones, and this migratory potential was enhanced following culture with IL-12. Migration was strongly inhibited by the F(ab')2 of an anti-NKRP1A Ab, suggesting that this lectin is involved in the migration process. We also show that, in freshly isolated PBMC from MS patients, the migrated population was enriched for V delta 2+ NKRP1A+ cells. We conclude that the expression of NKRP1A on V delta 2+ cells is associated with increased ability to migrate across the vascular endothelium and that this phenomenon may be regulated by IL-12 present in the microenvironment.
1999
01 Pubblicazione su rivista::01a Articolo in rivista
Interleukin-12 mediated NKRP1A upregulation and consequent enhancement of endothelial transmigration of Vd2+ TCRgd+ T lymphocytes from healthy donors and multiple sclerosis / Poggi, A; Zocchi, Mr; Costa, P; Ferrero, E; Borsellino, G; Placido, R; Galgani, S; Salvetti, Marco; Gasperini, Claudio; Ristori, Giovanni; BROSNAN CF AND BATTISTINI, L.. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 162:(1999), pp. 4349-4354.
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

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/11573/109183
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 65
  • ???jsp.display-item.citation.isi??? 64
social impact