Human NK Cell Subsets in Pregnancy and Disease: Toward a New Biological Complexity

Abstract

In humans, NK cells are mainly identified by the surface expression levels of CD56 and CD16, which differentiate between five functionally different NK cell subsets. However, nowadays NK cells are considered as a more heterogeneous population formed by various subsets differing in function, surface phenotype, and anatomic localization. In human CMV- and hantaviruses-infected subjects, an increased frequency of a NKG2A−CD57+NKG2C+ NK cell subset has been observed, while the phenotype of the NK cell subpopulation associated with cancer may vary according to the specific kind of tumor and its anatomical location. The healthy human lymph nodes contain mainly the CD56bright NK cell subset while in melanoma metastatic lymph nodes the CD56dimCD57+KIR+CCR7+ NK cell subpopulation prevails. The five NK cell subpopulations are found in breast cancer patients, where they differ for expression pattern of chemokine receptors, maturation stage, functional capabilities. In pregnancy, uterine NK cells show a prevalence of the CD56brightCD16− NK cell compartment, whose activity is influenced by KIRs repertoire. This NK cell subset’s super specialization could be explained by (i) the expansion of single mature CD56dim clones, (ii) the recruitment and maturation of CD56bright NK cells through specific stimuli, and (iii) the in situ development of tumor-resident NK cells from tissue-resident CD56bright NK cells independently of the circulating NK cell compartment. This new and unexpected biological feature of the NK cell compartment could be an important source of new biomarkers to improve patients’ diagnosis.

Porphyromonas gingivalisand adverse pregnancy outcome

“…− and express a repertoire of activating and inhibitory receptors (NKRs) that can fluctuate in response to EVT and invading pathogens [63]. Although the biological functions of uNK cells is still largely unknown, these cells appear to be important for spiral artery remodeling.…”

“…In a healthy pregnancy, most dNKs are CD56 bright cells that possess granules such as perforin and granzyme B but have low potential for degranulation and are mainly pro-angiogenic, cytokine secreting and immunomodulatory. Double-negative or CD56 dim populations have been described as secreting low levels of IFN-γ and TNF-α and having a detrimental impact on pregnancy [63]. A number of studies have found that alterations in dNK subsets are higher in cases of unexplained recurrent miscarriage, infertility, and implantation failure [81][82][83][84].…”

New avenues for melanoma immunotherapy: Natural Killer cells?

“…Notably, alterations in circulating NK cells frequency, phenotype and function have also been found in tumour patients and have been associated with the clinical outcome . So far, the analysis of peripheral blood NK cells in solid tumours patients showed an association between a suppressed functionally impaired NK cells phenotype and poor prognosis.…”

“…80 Notably, alterations in circulating NK cells frequency, phenotype and function have also been found in tumour patients and have been associated with the clinical outcome. [81][82][83][84][85][86][87][88][89][90] So far, the analysis of peripheral blood NK cells in solid tumours patients showed an association between a suppressed functionally impaired NK cells phenotype and poor prognosis. Peripheral NK cells from metastatic melanoma patients show an exhausted phenotype, with a high expression of KIRs, low levels of NCRs and downregulation of stimulating cytokines receptors, that result in functional defects in their ability to proliferate, secrete cytokines and kill target cells.…”

Heterogeneity of Nk and NKT Lymphocyte Populations in Healthy Donors

“…В ходе развития методов ис-следования оказалось, что данные популяции ге-терогенны и, в свою очередь, разделяются на не-сколько субпопуляций, способных выполнять как эффекторные, так и регуляторные функции. Нарушение баланса между этими субпопуля-циями происходит при многих заболеваниях, в том числе онкологических [7]. При изуче нии иммунофенотипа линейных популяций лимфо-цитов периферической крови первичных боль-ных раком яичников до и после хирургического лечения было обнаружено, что происходит на-рушение линейности, то есть у таких больных снижено количество Т-лимфоцитов по сравне-нию с контрольной группой доноров (62,5±3,1 и 73,9±2,5% соответственно), в том числе за счет повышения количества NK-лимфоцитов [4].…”