The role of natural killer (NK) cells in hematopoietic stem cell transplantation and in the control of neonatal infections is not yet clear. Donor-versus-recipient NK cell alloreactivity was found to improve outcome in some settings of hematopoietic stem cell transplantation. We hypothesized that the role of NK cells in cord blood (CB) transplantation and neonatal infections may depend on CB NK cell maturation stage. We therefore analyzed the expression of NK cell differentiation/phenotypic markers in human CB, as well as functional properties of purified CB NK cells. CD8 and CD57 expression was lower in CB than in adult NK cells. However, the expression of other differentiation markers was similar, as was cell surface density of CD56, the percentage of late NK cell precursors, interferon-␥ production, and the proliferative response of purified NK cells to IL-2. Spontaneous cytotoxic activity of purified CB NK cells against NK-sensitive targets was low but reached adult levels after treatment with IL-15. Expression of perforin and granzyme B was higher in CB NK cells (90 versus 58% and 86 versus 69%, respectively Natural killer (NK) cells are innate immune lymphocytes defined by their cell surface expression of the CD56 antigen without expression of the CD3 antigen. They display a broad anti-infectious and antitumor cytolytic activity. They can also secrete various cytokines, such as interferon (IFN)-␥ and other cytokines that regulate the immune response and hematopoiesis (1). Although NK cells play an important role early in the infectious cycle, at a time when specific immunity has not yet fully developed, their role in the defense of the neonate against infection has not been studied (2). It was demonstrated recently that NK cells play an important role in the outcome of clinical HLA-haploidentical hematopoietic stem cell transplantation (1,3). A positive effect of NK cell alloreactivity has also been reported in a series of unrelated hematopoietic stem cell transplantations (4). We, as several other groups, use cord blood (CB) as a source of stem cells in partially HLA-mismatched transplantation with outcomes similar to those observed in HLA-identical bone marrow transplantation (5-9). CB contains a higher percentage of NK cells than adult blood-, bone marrow-, or cytokine-mobilized peripheral blood stem cell grafts (10). It thus is tempting to speculate that neonatal/CB NK cells may play a role in CB transplantation as well as in the control of neonatal infections.Several markers of NK cell immaturity have been described. Among these is the level of cell-surface expression of CD56.

gp350 of Epstein-Barr virus (EBV) induces a strong immune response in EBV-infected individuals, but relatively little is known about the clinical relevance of this response in patients with different EBV-associated malignancies and other diseases. Using our gp350-expressing cell clones, we studied gp350-specific humoral immune responses in the sera of individuals with nasopharyngeal carcinoma (NPC), chronic symptomatic EBV infection (CEI), Hodgkin's disease (HD), acute infectious mononucleosis (IM) and healthy EBVseropositive individuals (HI). The titres of antibody-dependent cellular cytotoxicity (ADCC) antibodies were highest in HI followed by CEI, HD and NPC. EBV-neutralizing (NA) and gp350-specific IgG antibody profiles in these conditions were: CEI G HI G NPC G HD, whereas IgA titres were the highest in NPC sera followed by CEI and HD. The sera from IM patients were found to be negative for gp350-specific ADCC and IgA activities. Sera from HI were also negative for gp350-specific IgA. A significant positive correlation was found between serum gp350 IgA and viral capsid antigen IgA and a significant negative one between IgM and ADCC titres. High IgA titres were also found in CEI and EBV-genome positive HD in addition to NPC. Importantly, gp350-specific IgA titres were of prognostic value in NPC patients. Our data provide new insights about the clinical relevance of gp350-specific immune responses in these diseases.

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An NK cell activity-resistant human lymphoid T cell line (CEM-NKr) expressing the transfected Epstein-Barr virus (EBV) gp350 gene was used in membrane immunofluorescence (MIF) and antibody-dependent cellular cytotoxicity (ADCC) assays to analyze the gp350-specific humoral and ADCC responses in groups of EBV-seropositive persons. Results show that there is no correlation between gp350-specific ADCC-mediating antibody titers and MIF or EBV neutralizing antibody titers. For example, sera from patients in the acute phase of infectious mononucleosis, while positive by MIF assay or EBV neutralization test, were not reactive in the ADCC assay. Results also show that nasopharyngeal carcinoma (NPC) patients on MIF present high IgG titers against gp350 compared with healthy persons. Anti-gp350 IgA antibodies were detected in all groups tested; however, titers were highest in the NPC group.

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SUMMARYCytotoxic T lymphocytes (CTL) are key players to suppress viral load (VL) but CTL responses become compromised with progression of HIV-infection/AIDS. Some progressors develop MHC-unrestricted CTL with anti-CD4 + cytocidal activity. Immune activation status of these CTL and its significance in disease progression are unknown. To determine the relationship between VL and T cell activation, a crosssectional study was carried out using blood samples from 13 HIV-1-infected/AIDS patients at various stages of progression and seven age-matched seronegative controls. We examined expression of HLA-DR and CD38 activation markers on purified CTL. MHC-unrestricted killing by these CTL was also evaluated against uninfected, allogeneic CD4+ T cells as well as several human cell lines. The expression of activation markers correlated inversely ( r s = -0·91, P < 0·0001) with VL of the subjects. CTL effectors of these patients killed targets expressing or lacking CD4 + , independently of MHC class I recognition. Interestingly, the patients with higher VL showed an increased number of gd TCR-bearing CTL in blood and their MHC-unrestricted killing activity was blocked significantly ( P < 0·01) by gd TCRspecific monoclonal antibody. CD3 + T counts of these patients were also consistently subnormal. Inverse correlation between VL and CD8 + T cell activation markers seems to be an indicator of CTL-associated immunopathogenesis in HIV patients with elevated gd CTL in the peripheral blood.

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