Fetal natural killer cell function is suppressed

Abstract

Previous studies have reported reduced natural killer (NK) cell activity in cord blood (CB) compared with adult blood mononuclear cell populations. Using a non-radioactive killing assay, we have verified these findings suggesting that either the fetal NK cell function is suppressed or that these cells are functionally immature. We have shown that CB NK cells are functional, since activating them with cytokines known to activate adult NK cells [interleukin-2 (IL-2), IL-12 and IL-15] increased activation. However, resting the cells, which enhanced adult NK cell activity (P < 0.01), had no effect on fetal NK cells (P = 0.2). These results suggested that fetal NK cells have the capacity to kill, but this is suppressed in vitro. This hypothesis was strengthened by our observation that eight of nine CB mononuclear cell populations had their NK activity restored by freeze-thawing, whereas four of five adult peripheral blood mononuclear cells had a reduced killing ability on freeze-thawing. Freeze-thawing removes a population of cells that suppresses CB NK cell function. To determine which was the case we performed extensive phenotypic analysis of the CB populations pre- and post-freezing and found that the percentage of the CD3- CD56+ population within CB increased significantly (P < 0.0005 by paired t-test) with freezing, whereas freeze-thawing had no effect on this population within a normal adult peripheral blood mononuclear cell population. Our data suggest that within CB there is a population of cells, as yet undefined, which may be inhibiting NK cell function. This report therefore shows clear differences between NK cells within the adult periphery and in CB, and may lead to a better understanding of events occurring in vivo.

Cytotoxic Function of Umbilical Cord Blood Natural Killer Cells: Relevance to Adoptive Immunotherapy

“…Berg et al showed that cryopreservation of expanded NK cells reduced expression of NKG2D and TRAIL and NK cell cytotoxicity, although this effect could be reversed by exposure of NK cells to IL-2 [37]. However, Dominguez et al observed that CB MNCs had their NK activity were restored by freeze/thawing, suggesting that the cytotoxic capacity of fetal NK cells was suppressed in vitro [38]. The effect of cryopreservation on NK function of purified UCB NK cells compared to their adult counterparts awaits further study.…”

Immunological mechanisms of severe respiratory syncytial virus bronchiolitis

“…Deficient immune function in neonates is characterised by relatively deficient functioning of innate and antigenspecific immunity [49,56]. Defective functions of the cells of the innate immune system consist of delayed recruitment of neutrophils and monocytes to infected tissue and diminished natural killer cell cytotoxicity [57]. During the neonatal period antigen presentation by macrophages and dendritic cells is less efficient, possibly due to deficient IL-12 production, resulting in slow development of antigen-specific immunity [48,49,58].…”

Natural Killer Cells in Perinatally HIV-1-Infected Children Exhibit Less Degranulation Compared to HIV-1-Exposed Uninfected Children and Their Expression of KIR2DL3, NKG2C, and NKp46 Correlates with Disease Severity

“…This dysfunction or immaturity of neonatal NK cells may reduce the capacity of neonates to respond to viral infections (20,(23)(24)(25). The decreased function of cord blood and neonatal NK cells may be partly due to an undefined suppressive mechanism (19). A more recent study suggests that CD4 ϩ CD25 ϩ T regulatory cells could decrease NK cell production of IFN-␥ and perforin, most likely through a direct cell-to-cell interaction (26).…”

“…A more recent study suggests that CD4 ϩ CD25 ϩ T regulatory cells could decrease NK cell production of IFN-␥ and perforin, most likely through a direct cell-to-cell interaction (26). The phenotype of NK cells derived from cord blood is different from that seen in adults, most notably in the lack of CD57 expression found on many adult CD56 dim NK cells (19,27,28). Adult CD57 ϩ NK cells are thought to represent senescent cells that have proliferated in vivo (20,29,30).…”