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      Infection of infants with human herpesvirus type 6 may be associated with reduced allergic sensitization and T-helper type 2 development : HHV-6 infection and allergic sensitization in children

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          Abstract

          Epidemiological studies point to an inverse relationship between microbial exposure and the prevalence of allergic diseases. The underlying mechanism for this observation remains largely unknown, as well as the nature of the microbes involved. To investigate the effects of early infection with human herpesviruses (HHVs) on IgE formation and T-helper type 2 (Th2) development in infants. Serum was collected from children aged 18 months and assessed for IgE to common allergens and IgG to five common herpesviruses. Cord blood plasmacytoid dendritic cells (pDC) were exposed to HHV type 6 in vitro and mixed with allogeneic cord blood CD4(+) T cells. Cytokine levels were determined by ELISA and by flow cytometry. We found that children seropositive at 18 months of age to HHV type 6 were significantly less often IgE sensitized than seronegative children [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.009-0.68]. HHV type 6 also decreased the production of the Th2-associated cytokines IL-5 and IL-13 by CD4(+) T cells when co-cultured with allogeneic cord blood pDC. This was associated with an increased production of IFN-alpha by pDC exposed to HHV type 6. These data indicate that an early childhood infection with HHV type 6 could down-regulate Th2 responses and reduce IgE formation to common allergens in a young child.

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          Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon.

          We have identified two cell subsets in human blood based on the lack of lineage markers (lin-) and the differential expression of immunoglobulin-like transcript receptor 1 (ILT1) and ILT3. One subset (lin-/ILT3+/ILT1+) is related to myeloid dendritic cells. The other subset (lin-/ILT3+/ILT1+) corresponds to 'plasmacytoid monocytes'. These cells are found in inflamed lymph nodes in and around the high endothelial venules. They express CD62L and CXCR3, and produce extremely large amounts of type I interferon after stimulation with influenza virus or CD40L. These results, with the distinct cell phenotype, indicate that plasmacytoid monocytes represent a specialized cell lineage that enters inflamed lymph nodes at high endothelial venules, where it produces type I interferon. Plasmacytoid monocytes may protect other cells from viral infections and promote survival of antigen-activated T cells.
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            Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells.

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              How epidemiology has challenged 3 prevailing concepts about atopic dermatitis.

              We challenge 3 prevailing concepts in understanding atopic dermatitis using data from epidemiologic studies. First, we show that although atopy is associated with atopic dermatitis to some degree, its importance is not likely to be a simple cause-and-effect relationship, especially at a population level. Our epidemiologic data do not exclude a contributory role for IgE-mediated immunologic processes, especially in those with existing and severe disease. Second, evidence is presented that does not support a straightforward inverse relationship between infections and atopic dermatitis risk. A link, if present, is likely to be more complex, depending critically on the timing and type of infectious exposure. Third, recent evidence suggests that the risk of subsequent childhood asthma is not increased in children with early atopic dermatitis who are not also early wheezers, suggesting a co-manifestation of phenotypes rather than a progressive atopic march. Collectively, these observations underline the importance of epidemiologic studies conducted at a population level to gain a more balanced understanding of the enigma of atopic dermatitis.
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                Author and article information

                Journal
                Clinical & Experimental Allergy
                Wiley
                09547894
                13652222
                June 2010
                May 06 2010
                : 40
                : 6
                : 882-890
                Article
                10.1111/j.1365-2222.2010.03491.x
                20345999
                c59bf980-8202-439c-8096-d1496db0eb84
                © 2010

                http://doi.wiley.com/10.1002/tdm_license_1.1

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