IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of Vδ2+ TCRγδ+ T lymphocytes from healthy donors and multiple sclerosis patients

Alessandro Poggi, Maria Raffaella Zocchi, Paola Costa, Elisabetta Ferrero, Giovanna Borsellino, Roberta Placido, Simona Galgani, Marco Salvetti, Claudio Gasperini, Giovanni Ristori, Celia F. Brosnan, Luca Battistini

Research output: Contribution to journalArticle

Abstract

γδ 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 Vδ2+ γδ T cells coexpressing NKRP1A is significantly increased compared with healthy donors. Vδ2+ and Vδ1+ T cells were sorted from MS patients and healthy volunteers and cloned. At variance with Vδ1+ clones, all Vδ2+ 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 Vδ1+ clones. RNase protection assay showed that IL-12R β2 subunit transcript was significantly less represented in Vδ1+ than Vδ2+ clones. This finding may explain the different effect exerted by IL-12 on these clones. In transendothelial migration assays, Vδ2+ NKRP1A+ clones migrated more effectively than Vδ1+ 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 Vδ2+ NKRP1A+ cells. We conclude that the expression of NKRP1A on Vδ2+ 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.

Original languageEnglish
Pages (from-to)4349-4354
Number of pages6
JournalJournal of Immunology
Volume162
Issue number7
Publication statusPublished - Apr 1 1999

ASJC Scopus subject areas

  • Immunology

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