NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs

Abstract

Key Points Clonal-like expansion of NK cells in response to CMV infection causes stable imprints in the human KIR repertoire. Education by inhibitory KIRs promotes the expansion of NK cells, causing repertoire skewing and a bias for self-specific inhibitory KIRs.

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

“…showed that expression of NKG2C, an activating receptor for HLA‐E, was increased in individuals infected with the human cytomegalovirus (HCMV) and that NKG2C + cells expressed high level of KIRs 159. It was later demonstrated that these HCMV‐associated NKG2C + NK cells express self‐specific KIRs and account for the vast majority of adult KIR repertoire deviation toward self HLA class I 160. HCMV‐adapted NK cells lacking NKG2C expression were also reported, most of them expressing activating KIRs 160, 161.…”

“…It was later demonstrated that these HCMV‐associated NKG2C + NK cells express self‐specific KIRs and account for the vast majority of adult KIR repertoire deviation toward self HLA class I 160. HCMV‐adapted NK cells lacking NKG2C expression were also reported, most of them expressing activating KIRs 160, 161. Using a large NKG2C‐deficient cohort, it was recently demonstrated that adaptive NK cell responses could occur in the absence of both activating KIRs and NKG2C; however, these adaptive NK cells also largely display repertoire deviation toward self‐specific inhibitory KIR expression 162, 163.…”

Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity

“…We recently reported that past CMV infection is associated with stable imprints in the human killer cell immunoglobulin-like receptor (KIR) repertoire caused by clonal-like expansion of NK cells expressing selfspecific KIRs (Beziat et al 2013). An important characteristic of such expanded cells was their differentiated phenotype with high expression of CD57 and ILT-2.…”

“…In this age group, it is yet uncertain whether an inversed CD4/CD8 ratio corresponds to increased mortality and truly defines an IRP. Since natural killer (NK) cells have an important role in the defense against viral infections and display profound changes throughout the lifespan (Le Garff-Tavernier et al 2010;Biron et al 1996;Beziat et al 2013), we set out to examine whether expansion of CD8 + T cells seen in individuals with an inversed CD4/CD8 ratio is coupled to a parallel skewing of the NK compartment. NK cells belong to the innate arm of the immune system and provide a rapid first line of defense against viral infections and may also contribute to the clearance of transformed cells (Lanier 2005;Vivier et al 2008).…”

“…Thus, NK cells expressing the activating receptor NKG2C expand specifically during acute infection or viral reactivation in immunocompromised patients (Foley et al 2012;Kuijpers et al 2008;Lopez-Verges et al 2011). In some individuals, such expansions lead to imprints in the NK cell receptor repertoire that remain stable over several years also during viral latency (Beziat et al 2013).…”