Delayed Early Primary Visual Pathway Development in Premature Infants: High Density Electrophysiological Evidence

In the past decades, multiple studies have been interested in developmental patterns of the visual system in healthy infants. During the first year of life, differential maturational changes have been observed between the Magnocellular (P) and the Parvocellular (P) visual pathways. However, few studies investigated P and M system development in infants born prematurely. The aim of the present study was to characterize P and M system maturational differences between healthy preterm and fullterm infants through a critical period of visual maturation: the first year of life. Using a cross-sectional design, high-density electroencephalogram (EEG) was recorded in 31 healthy preterms and 41 fullterm infants of 3, 6, or 12 months (corrected age for premature babies). Three visual stimulations varying in contrast and spatial frequency were presented to stimulate preferentially the M pathway, the P pathway, or both systems simultaneously during EEG recordings. Results from early visual evoked potentials in response to the stimulation that activates simultaneously both systems revealed longer N1 latencies and smaller P1 amplitudes in preterm infants compared to fullterms. Moreover, preterms showed longer N1 and P1 latencies in response to stimuli assessing the M pathway at 3 months. No differences between preterms and fullterms were found when using the preferential P system stimulation. In order to identify the cerebral generator of each visual response, distributed source analyses were computed in 12-month-old infants using LORETA. Source analysis demonstrated an activation of the parietal dorsal region in fullterm infants, in response to the preferential M pathway, which was not seen in the preterms. Overall, these findings suggest that the Magnocellular pathway development is affected in premature infants. Although our VEP results suggest that premature children overcome, at least partially, the visual developmental delay with time, source analyses reveal abnormal brain activation of the Magnocellular pathway at 12 months of age.     

Ligation of ICAM-1 molecules inhibits target cell-induced granule exocytosis of IL-12-activated natural killer cells

The importance of cell adhesion molecules such as ICAM-1 is emphasized in cell-to-cell interactions that are critical in the generation of effective immune reactions. In this study, the involvement of ICAM-1 in natural killer (NK) cell activities was characterized in IL-12-activated human NK cells. To address the question of whether ligation of ICAM-1 molecules can modulate NK cell cytolytic activities, a 4-h (51)Cr-release assay was performed after pretreatment of NK cells with R6.5 mAb (anti-human ICAM-1 mAb). Ligation of membrane ICAM-1 molecules significantly inhibited IL-12-enhanced NK cytotoxicity against K562, and the pretreatment of neutralizing soluble ICAM-1 with R6.5 mAb blocked this inhibitory effect. The involvement of Ca(2+)-dependent granular exocytosis was evaluated. BLT esterase assay demonstrated that the ligation of ICAM-1 molecules inhibited granular exocytosis of NK cells. Additionally, the ICAM-1-mediated inhibition of Ca(2+) flux in NK cells was detected using Fluo-3AM, while the pretreatment of NK cells with R6.5 mAb did not affect conjugate formation between NK and K562 cells. Collectively, these results suggest that the signals transduced from ICAM-1 molecules might be sufficient to induce inhibitory effects on NK cells.     

Cytotoxicity of human peripheral lymphocytes in cell-mediated lympholysis; antibody-dependent cell-mediated lympholysis and natural cytotoxicity assays after mixed lymphocyte culture.

Lymphocytes that have been purified by Ficoll-Hypaque centrifugation lose antibody-dependent and natural cytotoxic activities upon culture in tissue culture medium supplemented with human plasma. However, stimulation of peripheral lymphocytes in the mixed leukocyte culture (MLC) appears to enhance killer (K) and natural killer (NK) activities in addition to generating cytotoxic T ymphocytes. Enhancement of NK and antibody dependent activities appears to correlate with cell division as measured by 3H-thymidine uptake. However, elimination of dividing cells in the MLC by addition of 5-bromodeoxyuridine has no effect on NK and K cells activities. Since this treatment abolishes cell-mediated lympholysis mediated by cytotoxic T lymphocytes, it is a useful probe for determining the relative activities of NK, K, and cytotoxic T lymphocyte effector cells after lymphocyte stimulation.     

婴儿围产期感染乙型肝炎病毒后各项血清学指标的动态变化

本文观察了102名新生儿出生后至18月龄的HBV血清学指标的动态变化,婴儿分成乙型肝炎疫苗按种组(63人)和对照组(39人), 观察期间HBsAg始终阴性的70名婴儿,出生后6、12和18月龄的抗-HBc阳性率依次为90％、30％和4.3％;而HBsAg阳转的27名婴儿,18月龄时抗-HBc全都阳性,但仅有6名婴儿在6月龄时测出IgM抗-HBc,疫苗接种组婴儿出生后1、3、6、12和18月龄的抗-HBs阳性率,依次为28.6％、76.2％、77。8％、82.5％和82.5％;对照组婴儿18月龄时抗-HBs阳性率仅为12.8％。     

人胎脾细胞IL-2和IL-6的产生及其与NK细胞功能发育的关系

人类胚胎发育时期,脾细胞IL-2和IL-6的产生及其与NK细胞功能发育关系的研究结果表明,胚胎20周龄前IL-2的活性和NK活性细胞基本缺乏,但可分泌低水平的IL-6;随个体发育,IL-2、IL-6的产生和NK细胞活性均逐渐增强,三者间呈直线正相关关系(r>0.86);出生前,IL-6的产生和NK细胞活性显著低于成人组(p<0.01),而IL-2的产生巳达成人水平(p>0.05)。最后,对在胚胎发育过程中IL-2和IL-6的产生,及其与NK细胞功能发育间的关系进行了讨论。     

Depressed natural killer cell activity in children with protein--calorie malnutrition. II. Correction of the impaired activity after nutritional recovery

Natural killer (NK) cell activity and responsiveness to interferon (IFN) were measured in the peripheral blood of infants having kwashiorkor or marasmus and of nutritionally recovered malnourished children. Depression of NK activity in the peripheral blood lymphocytes (PBLs) of the malnourished children was noted, while normal levels of activity were observed in the nutritionally recovered infants. Addition of exogeneous interferon in vitro potentiated the NK levels of PBLs from well-nourished and nutritionally recovered infants, but had either a nonsignificant impact on cells from the marasmic infants or a suppressive effect on the cells from infants with kwashiorkor. The success of exogenous interferon to potentiate the NK levels of PBLs from nutritionally recovered infants suggests that nutritional repletion corrects the impaired cellular responsiveness in these patients.     

人胎脾细胞IL—2和IL—6的产生及其与NK功能发育的关系

The production of IL-2, IL-6 by fetal splenic mononuclear cells (FSMC) and relationship between them and the ontogenetic development of natural killer cell function were studied in human fetal spleens. As a results, before 20 weeks of gestation, both IL-2 and NK cell activities were not measured, but IL-6 was done. It was found that IL-2, IL-6 and NK cell activities were increased with the gestational age, and shown that there were linear positive correlation between the activities of three ones above (r > 0.86). Before the birth, the induced IL-2 activity was the same as adult levels (p > 0.05), although both IL-6 production and NK activity in fetal spleens were significantly lower than that in adults (p < 0.01). Lastly, the production of IL-2, IL-6 in relation to the functional development of NK cells during the embryonic development was discussed.     

Neonatal screening for congenital adrenal hyperplasia in North-Eastern Italy: a report three years into the program

AIMS: To evaluate the incidence of congenital adrenal hyperplasia (CAH) in the Northern Italian population and the efficiency of the North-Eastern Italy screening program. To adjust cut-off levels for 17-hydroxyprogesterone (17-OHP) in relation to gestational age and birth weight, comparing the benefits in terms of reduction of recall rates with the two approaches and ultimately choosing the better of the two. SUBJECTS AND METHODS: Since September 2001, blood samples from neonates born in North-Eastern Italy have been screened with a fluoroimmunoassay method for 17-OHP determination (DELFIA). A preliminary cut-off level of > or = 30 nmol/l was set both for term and preterm newborns. The values of 17-OHP were analysed using statistical methods in relation to gestational age and birth weight in order to modify the cut-off on the basis of our data. RESULTS: After 33 months of screening we screened 128,282 newborns and detected 6 affected babies. During the first 8 months of screening among the recalled babies, 89.6 and 78.1% were preterm and low-birth-weight newborns, respectively, with a recall rate of 2.59% for premature neonates and of 4.94% for babies with birth weights < 2,500 g. We chose a new cut-off value of 50 nmol/l for preterm newborns only and, after 4 months, the recall rate was reduced to 0.83% for these infants and to 1.83% for low-birth-weight infants. CONCLUSION: After 33 months of screening for CAH in North-Eastern Italy, we report an incidence of 1:21,380. In 5 out of 6 affected babies, the diagnosis was established only after a positive screening test, which prevented a severe salt-wasting crisis in these babies. The cut-off level related to gestational age led to a significant reduction in the number of false-positives among preterm babies.We therefore intend to continue with the screening program for CAH in North-Eastern Italy, keeping a gestational-age-related cut-off in the hope that our data may encourage a national screening program for CAH.     

Decreased Memory B Cells and Increased CD8 Memory T Cells in Blood of Breastfed Children: The Generation R Study

BackgroundBreastfeeding provides a protective effect against infectious diseases in infancy. Still, immunological evidence for enhanced adaptive immunity in breastfed children remains inconclusive.ObjectiveTo determine whether breastfeeding affects B- and T-cell memory in the first years of life.MethodsWe performed immunophenotypic analysis on blood samples within a population-based prospective cohort study. Participants included children at 6 months (n=258), 14 months (n=166), 25 months (n=112) and 6 years of age (n=332) with both data on breastfeeding and blood lymphocytes. Total B- and T-cell numbers and their memory subsets were determined with 6-color flow cytometry. Mothers completed questionnaires on breastfeeding when their children were aged 2, 6, and 12 months. Multiple linear regression models with adjustments for potential confounders were performed.ResultsPer month continuation of breastfeeding, a 3% (95% CI -6, -1) decrease in CD27+IgM+, a 2% (95 CI % -5, -1) decrease in CD27+IgA+ and a 2% (95% CI -4, -1) decrease in CD27-IgG+ memory B cell numbers were observed at 6 months of age. CD8 T-cell numbers at 6 months of age were 20% (95% CI 3, 37) higher in breastfed than in non-breastfed infants. This was mainly found for central memory CD8 T cells and associated with exposure to breast milk, rather than duration. The same trend was observed at 14 months, but associations disappeared at older ages.ConclusionsLonger breastfeeding is associated with increased CD8 T-cell memory, but not B-cell memory numbers in the first 6 months of life. This transient skewing towards T cell memory might contribute to the protective effect against infectious diseases in infancy.     

Natural killer and lymphokine-activated killer cell functions in chronic myeloid leukemia

Summary The natural killer (NK) and lymphokine-activated killer (LAK) cell activities of peripheral blood lymphocytes from chronic myeloid leukemia (CML) patients in remission and from healthy donors have been studied. Regression analysis to compare both cytotoxic responses in individual donors and the frequency of LAK cell precursors was also carried out. About 42% of CML patients in remission showed low NK activity (less than the mean percentage NK activity of healthy donors — 2 SD) and were categorised as low NK responders. The stage of remission or the drugs used to bring about remission did not influence the NK status. The LAK activity of low NK as well as normal NK responder CML patients was significantly low against the NK-sensitive K562 cell line and the NK-resistant VIP (melanoma) and T-24 (bladder carcinoma) tumor targets, as assessed by linear regression analysis. Allogeneic leukemic cells were more resistant to killing, especially by patients' LAK cells. The frequency analysis of LAK cell precursors revealed a significant reduction in the LAK cell progenitor frequency in CML patients in remission.     

Plasma selenium in preterm and term infants during the first 12 months of life

The goal of the present study was to prospectively assess the plasma selenium (Se) concentrations of term and preterm infants during the first year of life in relation to gestational age and nutrition.

Blood specimens were collected from orally formula-fed preterm infants (gestational age < 32 weeks, birth weight < 1500 g): 1.) in hospital and 2.) corrected for gestational age parallel to healthy term breast and formula-fed infants at the ages of 1, 4 and 12 months. All infants were fed according to a standardized nutritional concept, solids and follow-up formula were introduced at the age of 4 months.

Plasma selenium in preterm infants in hospital was 11.7 (6.5–20.8) g/l and 11.6 (8.8–16.7) g/l at 4 weeks corrected for gestational age. At the age of 4 months plasma selenium was still significantly lower than in the other groups: Preterm infants: 17.1 (10.4–30.5) g/l; formula-fed term infants: 31.3 (24.3–47.5) g/l; breast-fed term infants: 45.6 (27.1–65.1) g/l). The levels of breast-fed infants were significantly higher than those of both formula-fed groups up until the introduction of solids.

Preterm infants had significantly low plasma selenium levels up until a postnatal age of at least 6 months. The levels were lower than those of term infants fed an identical unsupplemented infant formula during the first 4 months of life. These data support routine monitoring in hospital and selenium supplementation of preterm infants, preferably in hospital before discharge.     

Radiosensitivity of human natural killer cells: binding and cytotoxic activities of natural killer cell subsets

The sensitivity of human natural killer (NK) cell activities (both binding and killing) after exposure of peripheral blood mononuclear cells to different doses of gamma radiation was studied. A panel of monoclonal antibodies was used to identify the NK and T-lymphocyte subsets and to evaluate their radiosensitivity. Peripheral blood mononuclear cells were irradiated with low (2-6 Gy) and high (10-30 Gy) doses and NK cell binding and cytotoxic activity against K562 target cells were studied after 3 h and 48 h in culture. The primary damage to NK cell activity was identified at the postbinding level and affected mainly the lytic machinery. After 48 h culture postirradiation, an overall depression of cytotoxic activity was observed, but ionizing radiation produced either a selection of the more cytotoxic NK cell subsets, which therefore might be considered more resistant to radiation damage than the less cytotoxic NK cells, or a long-term stimulation of cytotoxic activity in surviving cells.     

In vivo administration of low-dose human interleukin-2 induces lymphokine-activated killer cells for enhanced cytolysis in vitro

We have examined the effect of the intradermal administration of IL-2 on the generation of natural killer (NK) cell and lymphokine-activated killer (LAK) cell activity. Peripheral blood mononuclear cells (PBMC) obtained from borderline lepromatous (BL) and lepromatous leprosy (LL) patients and normal volunteers prior to and after IL-2 injection were stimulated in vitro with IL-2 and their cytolytic activities compared against 51Cr labeled target K562 cells, Daudi cells, and monocytes. Before IL-2 administration, PBMC obtained from BL/LL patients and normal volunteers possessed similar levels of NK cell activity indicating that the NK cell activity of the BL/LL patients was intact. LAK cell activity was induced with IL-2 in vitro in both BL/LL patients and in normal volunteers. The level of LAK cell activity in BL/LL patients was, however, suboptimal. A single intradermal dose of 25 micrograms IL-2 had no effect on the phenotype of circulating mononuclear cells in either patients or normal volunteers. However, 6-12 days after IL-2 injection and subsequent restimulation of the PBMC with IL-2 in vitro, cytolytic activity of LAK cells obtained from the BL/LL patients was enhanced while cells from normal volunteers expressed the same high levels of activity as observed before IL-2 injection.     

Divergence in activation by poly I:C of human natural killer and killer cells

Summary Interferons consistently enhance spontaneous cellular cytotoxicity (SCC) mediated by natural killer (NK) cells. More controversial is the ability of interferons to enhance antibody-dependent cellular cytotoxicity (ADCC) mediated by killer (K) cells. Since NK and K cells appear to represent overlapping subpopulations of lymphocytes, the present study was undertaken to examine in greater detail the relationship between NK and K cell functional modulation by the potent interferon inducer, poly I:C. Utilizing peripheral mononuclear cells from a panel of 21 healthy individuals, treatment in vitro with poly I:C resulted in modulation of both SCC and ADCC. SCC was significantly enhanced in 52 of a series of 55 trials (95%), whereas ADCC was significantly enhanced in parallel in only 18 of the trials (33%). Cells which mediated enhanced ADCC were plastic-nonadherent, which is characteristic of K cells. SCC was consistently enhanced in all but two of the 14 individuals who were tested two or more times. By contrast, the ability of poly I:C to enhance ADCC varied between trials in 11 of these individuals. In the other three, ADCC enhancement never occurred. No correlation existed between SCC and ADCC augmentation despite use of the same target cell to assess the two lytic activities in parallel. Poly I:C exclusively enhanced SCC in 36 trials (65%) and exclusively enhanced ADCC in two trials (4%). Discordance between SCC and ADCC enhancement also occurred in three of eight trials (38%) in which lymphocytes were treated directly with interferon a. Results in long-term (18-h) ⁵¹Cr-release assays indicated that poly I:C accelerated the kinetics of ADCC without affecting the proportion of target cells lysed by K cells. By contrast, an increased proportion of target cells was killed by poly I:C-stimulated NK cells. These results suggest that the controversy concerning relative interferon effects upon NK and K cells derives from differences both quantitative and qualitative in nature. K cell activity is enhanced but at a relatively low frequency. Enhancement of NK cell activity is selective in the sense that it occurs independently of and with greater frequency than enhancement of K cell activity. Distinct biological mechanisms may, therefore, be involved in regulation and expression of NK and K cell activation by interferons.     

Plasma trace element (Se,Zn, Cu) concentrations in maternal and umbilical cord blood in Poland

Selenium (Se), copper (Cu), and zinc (Zn) concentrations were determined in plasma of 64 mothers at delivery, 58 nonpregnant women, 64 neonates, and 12 infants, aged 2–12 mo. Se and Zn concentrations in mothers at delivery were significantly lower, and Cu higher than in nonpregnant women. Mean Se and Cu concentrations in newborns were statistically lower than those in mothers at delivery, and Zn and Cu concentrations in preterm infants (n=13) were significantly higher than in fullterm infants (n=51). Maternal parity had no significant influence on the distribution of plasma trace element levels. No significant differences were observed in Se and Zn levels in maternal and cord blood plasma according to birth weight, contrary to maternal Cu concentration. Significant correlations were found between maternal and cord blood Se content, and between maternal plasma Cu concentration and birth weight of neonates.     

Renal carcinoma cell lines inhibit natural killer activity via the CD94 receptor molecule

MHC class I molecules protect normal and transformed cells from lysis by natural killer (NK) cells through recognition of receptors expressed on leucocytes. Defects in NK cell activity and lymphokine activated killer (LAK) cell generation have been previously demonstrated in patients with renal cell carcinoma (RCC). However, to date, the importance of NK receptor/MHC class I interactions for immune evasion by RCC cells has not been described. In this study, human RCC cell lines (HTB46, HTB47, ACHN, CRL 1933 and HTB44) were found to be susceptible to lysis by both NK cells and interleukin-15 (IL-15)-derived LAK cells from normal donors in vitro. However, when NK cells were co-cultured with RCC cells their expression of the CD94 NK receptor molecule was significantly increased and their cytolytic activity against RCC targets was reduced. The cytolytic activity of NK cells was restored by the addition of IL-15, which further augmented the expression of CD94 on CD56+ NK cells. Disruption of NK receptor-MHC class I interactions by the addition of blocking antibodies to CD94 had no effect on the lysis of K562 or HTB47 targets by NK cells. However, the sensitivity of HTB46 cells to NK-mediated lysis was increased by blocking the CD94 receptor molecule, but only when the NK cells had not been previously co-cultured with RCC cells. This was independent of the presence of IL-15. These results show that RCC cells can inhibit NK activity via CD94 and suggest that disruption of interactions between receptor and ligand on RCC cells in vivo may augment the immune response against tumours by innate effector cells.     

IL-12, IFN-gamma, and T cell proliferation to measles in immunized infants

Measles infection in infants is associated with severe complications, and secondary infections are attributed to generalized immunosuppression. Measles binding to its monocyte receptor down-regulates IL-12 which is expected to diminish Th1-like cytokine responses, including IFN-gamma. Whether young infants can be immunized effectively against measles is an important public health issue. We evaluated Ag-specific IL-12, IFN-gamma, and T cell responses of infants at 6 (n = 60), 9 (n = 46), or 12 mo (n = 56) of age and 29 vaccinated adults. IL-12 and IFN-gamma release by PBMC stimulated with measles Ag increased significantly after measles immunization in infants. IL-12 and IFN-gamma concentrations were equivalent in younger and older infants, but IL-12 concentrations were significantly lower in infants than in adults (p = 0.04). IL-12 production by monocytes was down-regulated by measles; the addition of recombinant human IL-12 enhanced IFN-gamma production by PBMC stimulated with measles Ag, but infant T cells released significantly less IFN-gamma than adult T cells under this condition. Of particular interest, the presence of passive Abs to measles had no effect on the specific T cell proliferation or IFN-gamma production after measles stimulation. Cellular immunity to measles infection and vaccination may be limited in infants compared with adults as a result of less effective IFN-gamma and IL-12 production in response to measles Ags. These effects were not exaggerated in younger infants compared with effects in infants who were immunized at 12 mo. In summary, infant T cells were primed with measles Ag despite the presence of passive Abs, but their adaptive immune responses were limited compared with those of adults.     

Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications

Abstract Background aims. Interest in natural killer (NK) cell-based immunotherapy has resurged since new protocols for the purification and expansion of large numbers of clinical-grade cells have become available. Methods. We have successfully adapted a previously described NK expansion method that uses K562 cells expressing interleukin (IL)-15 and 4-1 BB Ligand (BBL) (K562-mb15-41BBL) to grow NK cells in novel gas-permeable static cell culture flasks (G-Rex). Results. Using this system we produced up to 19 × 10(9) functional NK cells from unseparated apheresis products, starting with 15 × 10(7) CD3(-) CD56 (+) NK cells, within 8-10 days of culture. The G-Rex yielded a higher fold expansion of NK cells than conventional gas-permeable bags and required no cell manipulation or feeding during the culture period. We also showed that K562-mb15-41BBL cells up-regulated surface HLA class I antigen expression upon stimulation with the supernatants from NK cultures and stimulated alloreactive CD8 (+) T cells within the NK cultures. However, these CD3 (+) T cells could be removed successfully using the CliniMACS system. We describe our optimized NK cell cryopreservation method and show that the NK cells are viable and functional even after 12 months of cryopreservation. Conclusions. We have successfully developed a static culture protocol for large-scale expansion of NK cells in the gas permeable G-Rex system under good manufacturing practice (GMP) conditions. This strategy is currently being used to produce NK cells for cancer immunotherapy.     

Natural killer cells can enhance the proliferative responses of B lymphocytes

In addition to lytic activity against malignant and virally transformed target cells, recent evidence has suggested that natural killer (NK) cells can modulate immune activities such as the suppression of B cell responses through noncytotoxic means. Using human B cells and highly purified autologous NK cells, we have demonstrated that NK cells can substantially augment the proliferative responses of B cells stimulated with the surface immunoglobulin crosslinking agents anti-IgM or Staphylococcus aureus Cowan strain I (SAC). This "enhancer" activity of NK cells was quite potent and was observed at an NK:B cell ratio as low as 0.05. Peak blastogenic responses of B cells cocultured with NK cells in the presence of B cell activators were observed at 2-3 days, similar to the responses of B cells in the absence of NK cells. Using the inhibitor of DNA synthesis mitomycin C, we determined that B cells and not NK cells were proliferating in cocultures of these lymphocytes stimulated with SAC. Activated B cells neither prevented the lysis of the isotope-labeled NK-sensitive target cell line K562 nor formed conjugates with NK cells, suggesting that cell contact was not a prerequisite for the effect. These studies have further expanded the functional repertoire of NK cells to include enhancer as well as suppressor and lytic activities.     

Association of decreased natural and antibody-dependent cellular cytotoxicity and production of natural killer cytotoxic factor and interferon in neonates

Cord blood lymphocytes (CBL) were compared with adult peripheral blood lymphocytes (a-PBL) for their: (i) natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities, (ii) target-binding capacity, (iii) ability to induce soluble natural killer cytotoxic factor (NKCF), (iv) interferon (IFN)-, interleukin 2 (IL-2)-, and lectin-induced augmentation of NK activity, and (v) ability to produce IFN against tumor targets in vitro. CBL depleted of adherent cells and Percoll-separated, NK-enriched subpopulations demonstrated significantly lower NK, ADCC, and target-binding activities compared to a-PBL. CBL produced significantly lower levels of NKCF directed against K562 tumor targets in comparison with a-PBL. Although the NK activity of CBL was not stimulated by either IFN or IL-2 to the same levels shown by a-PBL, the percentage enhancement of cytotoxicity of CBL by IFN and IL-2 was greater than that of a-PBL. Lectin-induced enhancement of cytotoxicity was significantly greater for CBL in comparison with a-PBL. Further, the ability of CBL lymphocytes to produce IFN-gamma in vitro against K562 target cells was significantly lower than that of adult PBL. These studies suggest an association between decreased NK, ADCC, and target-binding activities, induction of NKCF and IFN production by CBL, and increased susceptibility of neonates to infection.