Intrahepatic and peripheral blood phenotypes of natural killer and T cells: differential surface expression of killer cell immunoglobulin-like receptors

PODHORZER, ARIEL; MACHICOTE, ANDRÉS; BELÉN, SANTIAGO; LAUFERMAN, LEANDRO; IMVENTARZA, OSCAR; MONTAL, SILVINA; MARCIANO, SEBASTIÁN; GALDAME, OMAR; PODESTA, LUIS G.; FAINBOIM, LEONARDO

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2018

0019-2805

Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood NK, NKT and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activatory marker NKp44. By contrast, a decrease of CD16 expression with a potential decreased capacity to perform ADCC was the main difference between liver and peripheral blood CD56dim NK cells. Liver T cells with an effector memory or terminally differentiated phenotype showed an increased frequency of MAIT cells, TCR γδ T cells and TCRαβ CD8+ cells, with few naive T cells. Most liver NK and T cells expressed the homing markers CD161 and CD244. Liver T cells revealed a unique expression pattern of KIR receptors, with increased degranulation abilityand higher secretion of IFN-γ. Thus, the liver possesses a large amount of memory and terminally differentiated CD8+ cells with a unique expression pattern of KIR activating receptors that have a potent functional capacity as well as a reduced amount of CCR7 that are unable to migrate to regional lymph nodes. These results are consistent with previous studies showing that liver T (and also NK) cells likely remain and die in the liver.