Difference in Response of NK Cell Activity in Newborns and Adults to IL‐2, IL‐12 and IL‐15

Abstract

The killing activity of cord blood mononuclear cells (cMNC) against cytomegalovirus (CMV)-uninfected and -infected fibroblasts was comparable to that of adult peripheral blood mononuclear cells (aPBMC). The killing activity of cMNC against K562 cells was significantly lower compared with that of aPBMC. Treatment of cMNC and aPBMC with interleukin-2 (IL-2), IL-12 or IL-15 significantly enhanced killing activity against K562 cells and CMV-uninfected and -infected cells. By comparison of cMNC with aPBMC, killing activity against the K562 cells of cMNC was augmented to the level of aPBMC when cultured with IL-2, IL-12 or IL-15. The killing activity of cMNC against CMV-uninfected and -infected fibroblasts did not increase to the level of adult PBMC by treatment with IL-2, IL-12 or IL-15. These data suggest that cord blood contains a functionally different NK cell subpopulation than that among adult NK cells.

Bovine neonate natural killer cells are fully functional and highly responsive to interleukin-15 and to NKp46 receptor stimulation

“…This suggests a crucial role of NKp46 in the activation of neonate NK cells and confirms that they are fully functional. In humans, cord blood NK cells are less functional [23, 26, 33, 38] because mononuclear cells produce less cytokines [41, 51, 52], but when stimulated in vitro with IL-12, IL-15 or IL-2, their effector functions are similar to those of adult NK cells [23, 26, 33, 38]. In ruminants, this does not seem to be the case as in goats [58], neonate splenocytes produce much more IL-12 than adult splenocytes when stimulated with TLR ligands.…”

“…A general feature of neonates is that they have an incompletely developed immune system which leads to an increased susceptibility to infections and a weak response to most vaccines [27, 33, 42, 53, 61]. However, in response to BCG vaccination, neonates can mount a potent T H 1 cell response [34] and acquire significant protection against the disease.…”

Natural killer cell cytotoxicity is deficient in newborns with sepsis and recurrent infections

“…At 19 weeks, NK cell-like activity can be detected both in fetal liver and spleen and by the 28th week it appears in the peripheral blood as well [44,46]. Previous studies have shown that at birth, healthy newborns have signi®cantly lower NK activity than adults [7,18]. Similarly the decreased NK (n 28) and newborns diagnosed with recurrent infections (n 8) or sepsis (n 15) compared to healthy adults (n 89), expressed as percentage kill values at dierent eector-target ratios Fig.…”

Treatment of leukemic relapse following unrelated umbilical cord blood transplantation with interleukin-2: potential for augmenting graft-versus-leukemia and graft-versus-host effects with cytokines

“…Incubation experiments have noted increased anti-tumor effects against K562 cells compared to marrow cells. 5,14 NK activity of cord blood, which may be important in the graft-versus-tumor effect, is also enhanced by interleukin-2 and interleukin-12.…”