Effect of CMV and Aging on the Differential Expression of CD300a, CD161, T-bet, and Eomes on NK Cell Subsets.

Nelson Lopez-Sejas,Raquel Tarazona,Fakhri Hassouneh,Beatriz Sanchez-Correa,Carmen Campos,Alejandra Pera,Rafael Solana

doi:10.3389/fimmu.2016.00476

Abstract

Natural killer (NK) cells are innate lymphoid cells involved in the defense against virus-infected cells and tumor cells. NK cell phenotype and function is affected with age and cytomegalovirus (CMV) latent infection. Aging affects the frequency and phenotype of NK cells, and CMV infection also contributes to these alterations. Thus, a reduction of CD56bright NK cell subpopulation associated with age and an expansion of memory-like NK cells CD56dimCD57+NKG2C+ probably related to CMV seropositivity have been described. NK cells express T-bet and Eomes transcription factors that are necessary for the development of NK cells. Here, we analyze the effect of age and CMV seropositivity on the expression of CD300a and CD161 inhibitory receptors, and T-bet and Eomes transcription factors in NK cell subsets defined by the expression of CD56 and CD57. CD300a is expressed by the majority of NK cells. CD56bright NK cells express higher levels of CD300a than CD56dim NK cells. An increase in the expression of CD300a was associated with age, whereas a decreased expression of CD161 in CD56dim NK cells was associated with CMV seropositivity. In CD56dim NK cells, an increased percentage of CD57+CD300a+ and a reduction in the percentage of CD161+CD300a+ cells were found to be associated with CMV seropositivity. Regarding T-bet and Eomes transcription factors, CMV seropositivity was associated with a decrease of T-bethi in CD56dimCD57+ NK cells from young individuals, whereas Eomes expression was increased with CMV seropositivity in both CD56bright and CD56dimCD57+/− (from middle age and young individuals, respectively) and was decreased with aging in all NK subsets from the three group of age. In conclusion, CMV infection and age induce significant changes in the expression of CD300a and CD161 in NK cell subsets defined by the expression of CD56 and CD57. T-bet and Eomes are differentially expressed on NK cell subsets, and their expression is affected by CMV latent infection and aging.

Highlights

Natural killer (NK) cells are lymphocytes of innate immune response responsible for killing virus-infected cells and tumor cells
We analyzed by flow cytometry the expression of CD300a and CD161 inhibitory receptors on NK cells (CD56bright and CD56dim) from healthy individuals stratified by age and CMV latent infection
The expression of CD161 on CD56bright NK cells was not affected by CMV seropositivity in young donors, whereas it was decreased in middle age CMVseronegative individuals

Summary

Introduction

Natural killer (NK) cells are lymphocytes of innate immune response responsible for killing virus-infected cells and tumor cells. The expression of different receptors on NK cells is altered in aging [16,17,18] It has been found a decrease in the expression of natural cytotoxicity receptors (such as NKp30 and NKp46) and activating receptor DNAM-1 on CD56dim NK subset [3, 19,20,21] an increased expression of CD57 [18, 20, 22], as well as reciprocal changes in NKG2A and killer immunoglobulin-like (KIR) inhibitory receptors, associated with age [18, 20, 22]

Methods

Results

Conclusion