IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of V delta 2(+) TCR gamma delta(+) T lymphocytes from healthy donors and multiple sclerosis patients

gamma delta T lymphocytes are thought to play a role in the pathogenesis of multiple sclerosis (MS) contributing to demyelinization and fibrosis in th e 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 ce lls coexpressing NKRP1A is significantly increased compared with healthy do nors. V delta 2(+) and V delta 1(+) T cells were sorted from MS patients an d 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. RNas e protection assay showed that IL-12R beta 2 subunit transcript was signifi cantly less represented in V delta 1(+) than V delta 2(+) clones, This find ing may explain the different effect exerted by IL-12 on these clones. In t ransendothelial migration assays, V delta 2(+) NKRP1A(+) clones migrated mo re effectively than V delta 1(+) clones, and this migratory potential was e nhanced following culture with IL-12, Migration was strongly inhibited by t he 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 endotheli um and that this phenomenon may be regulated by IL-12 present in the microe nvironment.