Hajime Kimata

Modulation of ongoing human immunoglobulin synthesis by natural killer cells

Freshly separated human NK cells (NKH-1+) inhibited IgE synthesis from IgE myeloma U266/AF-10 as much as 70% whereas they enhanced IgG and IgA synthesis 200 and 500% from the lymphoblastoid cell lines GM-1500 and GM-1056, respectively. The inhibition of IgE synthesis by NK cells was due to a direct cytolytic effect on AF-10. This could be reversed using K562 cells in a cold target competition assay. NK cells also inhibited spontaneous IgE as well as IgG and IgA synthesis from B cells of highly atopic donors. On the other hand the enhancement of Ig secretion by NKH-1+ cells was shown to be mediated by soluble factors released from NK cells. Furthermore when NK cells were preincubated with immune complexes (IgE-IC) constructed of human IgE and mouse IgG1 monoclonal anti-human IgE, inhibition of IgE synthesis was reversed, and in some cases actual enhancement of IgE synthesis was observed, while enhancement of IgG and IgA synthesis was not affected. In contrast to NK cells, T cells depleted of NK cells (T-NK), when activated by IgE-IC, suppressed IgE synthesis in an isotype specific fashion. Thus, NK and T-cell modulation of ongoing Ig synthesis involve distinct mechanisms.

Enhancement of Allergic Skin Wheal Responses by Microwave Radiation from Mobile Phones in Patients with Atopic Eczema/Dermatitis Syndrome

Microwave radiation from mobile phones enhanced skin wheal responses induced by house dust mite and Japanese cedar pollen while it had no effect on wheal responses induced by histamine in patients with atopic eczema/dermatitis syndrome (AEDS). Microwave radiation also increased plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP) in patients with AEDS. These results indicate that microwave radiation from mobile phones may enhance allergen-induced wheal responses in association with the release of SP and VIP. This finding may be useful in elucidating the pathophysiology and treatment of AEDS.

Human natural killer (NK) cells produce a late-acting B-cell differentiation activity

The supernatant of unstimulated purified NKH-1 bearing human natural killer (NK) cells was found to enhance ongoing immunoglobulin synthesis. This NK-Cell supernatant (NKSN) enhanced IgE, IgG, and IgA synthesis from corresponding B-cell lines without increasing thymidine incorporation or cell number. Separation of NKH-1+ cells into CD3- or CD3+ cells showed that this activity was produced by the CD3- population. Recombinant human interleukin (IL)-1, IL-2, IL-4, interferon (INF)-beta 1, INF-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, or partially purified low molecular weight B-cell growth factor (BCGF) failed to provide the same enhancement of Ig synthesis. While the NKSN contained small amounts of IL-6 (0.1 U/ml) and IL-6 could increase Ig synthesisin vitro, the optimal IL-6 enhancement was far less than that observed with NKSN. NKSN also enhanced ongoing Ig synthesis fromin vivo activated B cells obtained from peripheral blood or bone marrow but failed to induce Ig synthesis from resting orin vitro activated B cells. These results demonstrate that human NK (CD3-, NKH-1+) cells can produce B-cell differentiation activity capable of regulating Ig productionin vivo, which appears to be distinct from the activity of previously described cytokines.

Enhancement of Allergic Skin Responses by Total Sleep Deprivation in Patients with Allergic Rhinitis

Atopic patients often complain of sleep disturbance caused by allergic symptoms or mental stress. It has been reported that in normal donors, partial sleep deprivation together with strenuous exercise or total sleep deprivation decreases natural killer cell numbers and plasma interleukin-6 levels, while it increases neutrophil numbers and plasma granulocyte-macrophage colony-stimulating factor levels [1, 2]. However, the effect of sleep deprivation on allergic responses in atopic patients has not been reported. I examined the effect of total sleep deprivation on allergen-induced skin wheal responses in patients with

Enhancement of IgE production in B cells by neutrophils via galectin-3 in IgE-associated atopic eczema/dermatitis syndrome.

Spontaneous IgE production by B cells from patients with IgE-associated atopic eczema/dermatitis syndrome (AEDS) is enhanced by polymorphonuclear leukocytes (PMN) from patients with AEDS, but not by PMN from non-atopic controls. The enhancement is abolished by preincubation of PMN with lactose, but not with glucose. Anti-galectin-3 serum, but not control rabbit serum, blocked the enhancement. These results indicate that AEDS PMN can enhance IgE production via galectin-3.

Suckling Reduces Allergic Skin Responses and Plasma Levels of Neuropeptide and Neurotrophin in Lactating Women with Atopic Eczema/Dermatitis Syndrome

Background: Lactation is associated with an inhibited hypothalamic-pituitary-adrenal axis response to physical and psychological stress in women and female rats. However, suckling also improved mood and calmness in nonatopic lactating women. Relaxation by humor reduced allergen-induced skin wheal responses, while various forms of stress enhanced those responses in allergic patients. Moreover, enhancement and reduction in allergen-induced skin wheal responses are associated with up- and down-regulation of plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP), respectively. In addition, plasma levels of SP, VIP and nerve growth factor (NGF), but not neurotrophin-3 (NT-3), are elevated in allergic patients. Therefore, the effects of suckling on allergic responses and plasma levels of neuropeptides and neurotrophins were studied in lactating women with atopic eczema/dermatitis syndrome (AEDS). Methods: Before and after suckling, allergic skin responses to allergens were studied by skin prick test; simultaneously plasma levels of substance P, vasoactive intestinal peptide, nerve growth factor and neurotrophin-3 were measured in lactating women with atopic eczema/dermatitis syndrome. Results: Suckling reduces allergen-induced, but not histamine-induced, skin wheal responses, while holding infants without suckling failed to do so. Suckling also reduced plasma levels of SP, VIP and NGF, but not NT-3 in these patients, while holding infants without suckling failed to do so. Conclusions: These results indicate that suckling reduces allergic responses with a concomitant reduction in plasma levels of SP, VIP and NGF. Collectively, suckling may have some implication in the study of maternal allergy in atopic patients.

Functional human T cell-B cell hybridomas established from fusion of normal T cells and an EBV-transformed B cell line☆

Human T cell-B cell hybridomas containing 92 chromosomes were derived by fusing normal stimulated CD-depleted T cells with the EBV-transformed human B cell line 729-HF. These hybridomas coexpressed the T cell surface markers CD3, CD8, and CD2 and the B cell surface antigens CD19, CD20, CD23, DR, and DQ. They weakly and variably expressed surface IgM and TCR. Genomic analysis revealed the presence of rearranged Ig genes as well as beta-T cell receptor genes that could be ascribed to the B and T cell parent, respectively. Analysis of TCR rearrangement suggests that the T-B hybridomas are, in fact, subclones of a single dominant clone. Although the hybrids expressed CD8 and not CD4, following preincubation with PWM, some the of clones induced IgG synthesis from normal B cells while the parent B cell line failed to demonstrate this activity. Stimulation of the hybridomas with PMA down-regulated the T cell lineage-specific antigen display (CD3, CD8, and TCR) and increased IgM production from the hybrids without changing B cell surface antigen display. These hybridomas may be useful to dissect the steps involved in the ultimate commitment of a cell to the B or T cell lineages and will be made available to interested investigators.