Cutaneous Immunization Rapidly Activates Liver Invariant Vα14 NKT Cells Stimulating B-1 B Cells to Initiate T Cell Recruitment for Elicitation of Contact Sensitivity

T cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating process mediated by B-1 cells that produce IgM, which activates complement to promote T cell passage into the tissues. We now show that Vα14i NKT cells induce B-1 cell activation likely by releasing IL-4 early postimmunization. The CS initiation process is absent in Jα18−/− and CD1d−/− NKT cell–deficient mice and is reconstituted by populations enriched for Vα14i NKT cells. Transfers are not effective if cells are derived from IL-4−/− mice. Staining with specific tetramers directly showed that hepatic Vα14i NKT cells increase by 30 min and nearly double by 2 h postimmunization. Transfer of immune B-1 cells also reconstitutes CS responses in NKT cell–deficient mice. The B-1 cells act downstream of the Vα14i NKT cells to restore CS initiation. In addition, IL-4 given systemically to Jα18−/− or CD1d−/− NKT cell–deficient mice reconstitutes elicitation of CS. Further, splenocytes from immune Jα18−/− mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized WT mice. Together these findings indicate that very early after skin immunization Vα14i NKT cells are stimulated to produce IL-4, which activates B-1 cells to produce Ag-specific IgM, subsequently needed to recruit effector T cells for elicitation of CS responses

Maternal socio-demographic and psychological predictors for risk of developmental delays among young children in Mongolia

Abstract Background Factors influencing child development are not well studied in developing settings, and especially in Mongolia. This cohort study examined the relationship between maternal socio-demographic and psychological conditions on risk of young child developmental delay. Methods A total of 150 children aged between 13 ~ 24 months old participated in this study. The participants were randomly selected from a pre-existing cohort of 1297 children who were involved in a study on infant bilirubin nomogram development conducted at a tertiary health facility in Mongolia between 2012 and 2013. Child development was evaluated using the Mongolian Rapid Baby Scale (MORBAS), a validated scale for child development. The potential factors for child developmental delay were assessed using a pre-tested questionnaire comprising of 52 questions. Fisher’s exact test and multivariable logistic regression analysis were conducted. Results Seventeen (11%) out of the 150 children that participated in the study were at risk of developmental delay. There was a negative association between the risk of child developmental delay and higher maternal education (AOR 0.15, 95% CI: 0.03–0.66). Increasing maternal age (AOR 1.12, 95%CI: 0.98–1.27), maternal depression symptoms (AOR 4.93, 95%CI: 0.93–26.10), child gender being female (AOR 0.25, 95%CI: 0.06–1.00) and being from single mother household (AOR 0.14, 95%CI: 0.01–1.11) were also predictors for risk of developmental delay – although the association was marginal. Conclusions Our findings suggest that being of underprivileged social status, and poor psychological condition of mothers in Mongolia possibly increases the risk of child developmental delays. Interventions targeting these modifiable predictors are needed to develop prevention strategies for child developmental delay

B cell-dependent T cell responses: IgM antibodies are required to elicit contact sensitivity.

Contact sensitivity (CS) is a classic example of in vivo T cell immunity in which skin sensitization with reactive hapten leads to immunized T cells, which are then recruited locally to mediate antigen-specific inflammation after subsequent skin challenge. We have previously shown that T cell recruitment in CS is triggered by local activation of complement, which generates C5a that triggers C5a receptors most likely on mast cells. Here, we show that B-1 cell-derived antihapten IgM antibodies generated within 1 day (d) of immunization combine with local challenge antigen to activate complement to recruit the T cells. These findings overturn three widely accepted immune response paradigms by showing that (a) specific IgM antibodies are required to initiate CS, which is a classical model of T cell immunity thought exclusively due to T cells, (b) CS priming induces production of specific IgM antibodies within 1 d, although primary antibody responses typically begin by day 4, and (c) B-1 cells produce the 1-d IgM response to CS priming, although these cells generally are thought to be nonresponsive to antigenic stimulation. Coupled with previous evidence, our findings indicate that the elicitation of CS is initiated by rapidly formed IgM antibodies. The IgM and challenge antigen likely form local complexes that activate complement, generating C5a, leading to local vascular activation to recruit the antigen-primed effector T cells that mediate the CS response