NKp44/HLA-DP-dependent regulation of CD8 T cell clonality by NK cells. NKp44/HLA-DP-dependent regulation of CD8 T cell clonality by NK cells

NK cells are increasingly recognized for their modulation of adaptive T cell responses; however the mechanisms by which NK cells modulate immune responses in human are unclear. Here we report that NKp44+ NK cells regulate CD8+ T cell expansion in an HLA-DP haplotype-dependent process. HLA-DP expression was significantly upregulated on CD8+ effector T cells, in particular in HCMV+ individuals. NK cells were activated in vitro through NKp44 by HLA-DP+ CD8+ T cells expressing NKp44-binding HLA-DP haplotypes. In individuals homozygous for non-NKp44-binding HLA-DP haplotypes, larger frequencies of HLA-DP+ CD8+ T cells were observed, and these specifically included hyper-expanded CD8+ T cell clones that were not observed in individuals encoding for NKp44-binding HLA-DP haplotypes. These data identify a pathway by which NKp44+ NK cells can edit CD8+ T cell effector populations in an HLA-DP haplotype-dependent process and prevents the generation of hyper-expanded T cell clones, which have been suggested to have increased potential for autoimmunity.