Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases

Figure 3

Natural killer cells in type1 diabetes. Several in vivo studies correlate NK cells to diabetes progression: an in vivo model of coxsackievirus B4- (CVB4-) induced diabetes showed that NK antiviral defence resulted in a reduced permissiveness to infection and subsequent NK cell-dependent death (a). Anti-CTLA-4 mAb treatment of T cell receptor transgenic mice demonstrated that higher frequency of NK cells induces aggressive insulitis, resulting in b-islet cell destruction (b). A protective role of NK cells was reported in NOD mice undergoing complete Freund’s adjuvant (CFA). NOD/SCID mice immunized with CFA recover its protective effects when CD3⁻DX5⁺ NKs are adoptively transferred into animal recipients, by downregulating autoreactive T cell response (c). In human samples, lower expression of the NKp30 and NKp40 was detected in type 1 diabetic patients as compared with control. Type 1 diabetic patients display an increased frequency of KIR gene haplotypes, including the activating KIR2DS3 gene, with a genetic interaction between the KIR and HLA complexes (d).

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