Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptors

Neutral evolution in paroxysmal nocturnal hemoglobinuria

“…Thus, the expansion of GPI Ϫ cells characteristic of PNH may be the consequence of a selective immune attack against normal (GPI ϩ ) HSCs to which PNH (GPI) HSCs are invulnerable (5). In recent years considerable evidence has accumulated in favor of such an autoimmune mechanism (48)(49)(50)(51)(52)(53). Perhaps the most specific evidence is that in PNH patients CD8ϩ CD57ϩ T cells are oligoclonal; and in more than two-thirds of patients, there are T cells bearing a set of highly homologous TCR molecules (53).…”

Human Invariant NKT Cells Display Alloreactivity Instructed by Invariant TCR-CD1d Interaction and Killer Ig Receptors

“…Because clone NKVFS1, the mAb used in our assays, binds with equal affinity to most if not all KIR2D isoforms (32,33,46), the enhanced and dynamic expression of KIR in the allogeneic setting could reflect up-regulation of either inhibitory or activating KIR. The functional assays used in the presence of the anti-KIR mAb suggested very strongly that, during the course of the iNKT cell MLR, in functional terms the activating KIR prevailed over inhibiting KIR and are very important determinants in the allogeneic activation of iNKT cells.…”

“…The anti-KIR clones used (either purified or as supernatants) have been described previously (32,33) and were as follows: the pan-anti-KIR2D (CD158abjhi) clone NKVFS1, anti-CD158b/j clone GL183, anti-CD158e clone Z27, and anti-CD158i clone FES172. The following mouse anti-human mAbs were also used: FITC-, R-phycoerythrin (RPE)-, or biotin-labeled anti-TCRV␣24 and TCRV␤11 (Serotec; Beckman Coulter); CD3-allophycocyanin, IgG1-FITC, IgG1-RPE, and IgG1-biotin (Caltag Laboratories); CD3-PerCP, HLA-DR-allophycocyanin, streptavidin-allophycocyanin, and PE-labeled anti-invariant TCRV␣J␣18 chain clone 6B11 (BD Biosciences).…”

“…To confirm that during the course of the allogeneic activation of iNKT cells activating KIR indeed prevail over inhibiting ones, we used a re-directed cell lysis assay (33,38) in which the anti-pan-KIR2D mAb was used to cross-link KIR on iNKT cells with the Fc receptors of the P815 mastocytoma cells (Fig. 5D).…”

Paroxysmal Nocturnal Hemoglobinuria

“…Functionally, these pathogenic T cells harbor an effector, cytotoxic phenotype, characterized by expression of CD8 and CD57. These effector lymphocytes also show an imbalance in the expression of the activating and inhibitory surface receptors; in fact, they tend to over-express the activating isoforms of inhibiting superfamily receptors, which elicit a powerful cytolytic activity (Poggi et al 2005). Notably, in some PNH patients these CTL clonal populations may expand to represent a subclinical (Risitano et al 2005) or even clinically meaningful LGL proliferations (Karadimitris et al 2001).…”