Most iKIRs recognize HLA class I ligands and function as important receptors in the maintenance
of NK-cell self-tolerance. In contrast, neither the ligands nor the function of most aKIRs have been established . We haverecently shown in patients undergoing solid organ transplantation a protective effect of B haplotype genes regarding posttransplant CMV infection and reactivation [5, 6]. Similar studies have shown congruent results for donor activating KIR genotype in recipients of hematopoietic stem cell transplantation [7, 8]. These data suggest that NK cells might recognize CMV-infected cells via activating KIR receptors. Primary CMV infection most frequently occurs subclinically, and no studies have so far studied Temozolomide price NK cells during primary CMV infection. However, recent evidence suggests that murine NK cells may display immunological memory comparable to that of B and T lymphocytes [9, 10]. In mice infected with murine CMV, the repertoire of Ly49 (the murine homologue of KIR) on NK cells stays permanently altered . The potential for CMV to modulate NK-cell surface receptors is underlined by the fact that in humans, latent CMV infection has been shown to induce permanent up-regulation of the activating NK-cell receptor natural
killer cell group antigen 2C (NKG2C) [12-14]. Collectively, these data suggest that latent CMV infection might lead to changes in the KIR repertoire of NK cells or might alter the NK-cell response to CMV in vitro. We therefore assessed in a cohort of healthy donors the expression of inhibitory and activating KIR receptors. KIR Hydroxychloroquine chemical structure repertoire was assessed both in freshly collected NK cells as well as after Selleckchem AZD5363 co-culture with a CMV-infected fibroblast cell line. Fifty-four healthy donors were genotyped for the nonframework genes 2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, and 3DS1. KIR gene frequencies were comparable in 23 CMV-seropositive and 31 seronegative
donors and within the range of published prevalences for Caucasian donors (data not shown). The expression of cell surface inhibitory (2DL1/CD158a, 2DL2/3/CD158b, 2DL5/CD158f, 3DL1/CD158e1) and activating (2DS1/CD158h, 2DS4/CD158i, 3DS1/CD158e2) KIRs by flow cytometry was equally comparable between CMV-seronegative and CMV-seropositive patients (Supporting Information Fig. 1A–E, H and J). No antibodies are available against KIR2DS3 and KIR2DS5, and all antibodies that detect KIR2DS2 cross-react with the inhibitory isoform KIR2DL2. We therefore used quantitative PCR to compare the expression of these receptors in purified NK cells from CMV-seropositive and -seronegative donors. Again, no significant differences were detected between CMV-seropositive and CMV-seronegative donors for KIR2DS2, KIR2DS3, or KIR2DS5 (Supporting Information Fig. 1F, G and I). Previous data demonstrated the expansion of NK cells expressing the activating receptor NKG2C in CMV-seropositive donors .