Killer Immunoglobulin-like Receptors

• Published in: Immunity & ageing 2013-08, Vol.10
• Main Authors: Rea, Irene Maeve, Maxwell, Lynn D, McNerlan, Susan E, Alexander, H Denis, Curran, Ma, Middleton, Derek, Ross, Owen A
• Format: Article
• Language: English
• Subjects: Aged; Aging; Analysis; Antigens; Cytokines; Genetic aspects; Immunotherapy; Killer cells; Physiological aspects; Receptor antibodies; Transforming growth factors
• ISSN: 1742-4933; 1742-4933
• DOI: 10.1186/1742-4933-10-35

Background Natural Killer Cells (NK) play an important role in detection and elimination of virus-infected, damaged or cancer cells. NK cell function is guided by expression of Killer Immunoglobulin-like Receptors (KIRs) and contributed to by the cytokine milieu. KIR molecules are grouped on NK cells into stimulatory and inhibitory KIR haplotypes A and B, through which NKs sense and tolerate HLA self-antigens or up-regulate the NK-cytotoxic response to cells with altered HLA self-antigens, damaged by viruses or tumours. We have previously described increased numbers of NK and NK-related subsets in association with sIL-2R cytokine serum levels in BELFAST octo/nonagenarians. We hypothesised that changes in KIR A and B haplotype gene frequencies could explain the increased cytokine profiles and NK compartments previously described in Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST) octo/nonagenarians, who show evidence of ageing well. Results In the BELFAST study, 24% of octo/nonagenarians carried the KIR A haplotype and 76% KIR B haplotype with no differences for KIR A haplogroup frequency between male or female subjects (23% v 24%; p=0.88) or for KIR B haplogroup (77% v 76%; p=0.99). Octo/nonagenarian KIR A haplotype carriers showed increased NK numbers and percentage compared to Group B KIR subjects (p=0.003; p=0.016 respectively). There were no KIR A/ B haplogroup-associated changes for related CD57+CD8 (.sup.high or low) subsets. Using logistic regression, KIR B carriers were predicted to have higher IL-12 cytokine levels compared to KIR A carriers by about 3% (OR 1.03, confidence limits CI 0.99-1.09; p=0.027) and 14% higher levels for TGF-[beta] (active), a cytokine with an anti-inflammatory role, (OR 1.14, confidence limits CI 0.99-1.09; p=0.002). Conclusion In this observational study, BELFAST octo/nonagenarians carrying KIR A haplotype showed higher NK cell numbers and percentage compared to KIR B carriers. Conversely, KIR B haplotype carriers, with genes encoding for activating KIRs, showed a tendency for higher serum pro-inflammatory cytokines compared to KIR A carriers. While the findings in this study should be considered exploratory they may serve to stimulate debate about the immune signatures of those who appear to age slowly and who represent a model for good quality survivor-hood. Keywords: Ageing, BELFAST octo/nonagenarians, KIR A and B haplotypes, Cytokines, IL-6, IL-12, IL-12p40, IL-10, Active TGF-[beta], sIL-2R, TNF-[alpha]