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BackgroundWhile the human fetal immune system defaults to a program of tolerance, there is concurrent need for protective immunity to meet the antigenic challenges encountered after birth. Activation of T cells in utero is associated with the fetal inflammatory response with broad implications for the health of the fetus and of the pregnancy. However, the characteristics of the fetal effector T cells that contribute to this process are largely unknown.MethodsWe analyzed primary human fetal lymphoid and mucosal tissues and performed phenotypic, functional, and transcriptional analysis to identify T cells with pro-inflammatory potential. The frequency and function of fetal-specific effector T cells was assessed in the cord blood of infants with localized and systemic inflammatory pathologies and compared to healthy term controls.ResultsWe identified a transcriptionally distinct population of CD4+ T cells characterized by expression of the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF). PLZF+ CD4+ T cells were specifically enriched in the fetal intestine, possessed an effector memory phenotype, and rapidly produced pro-inflammatory cytokines. Engagement of the C-type lectin CD161 on these cells inhibited TCR-dependent production of IFNγ in a fetal-specific manner. IFNγ-producing PLZF+ CD4+ T cells were enriched in the cord blood of infants with gastroschisis, a natural model of chronic inflammation originating from the intestine, as well as in preterm birth, suggesting these cells contribute to fetal systemic immune activation.ConclusionOur work reveals a fetal-specific program of protective immunity whose dysregulation is associated with fetal and neonatal inflammatory pathologies.

Introduction In a healthy human pregnancy, fetal immunity is uniquely adapted both to promote tolerance in utero and to subsequently provide protection after birth. Unlike in mice, which lack peripheral [...], BACKGROUND. While the human fetal immune system defaults to a program of tolerance, there is a concurrent need for protective immunity to meet the antigenic challenges encountered after birth. Activation of T cells in utero is associated with the fetal inflammatory response, with broad implications for the health of the fetus and of the pregnancy. However, the characteristics of the fetal effector T cells that contribute to this process are largely unknown. METHODS. We analyzed primary human fetal lymphoid and mucosal tissues and performed phenotypic, functional, and transcriptional analysis to identify T cells with proinflammatory potential. The frequency and function of fetal-specific effector T cells was assessed in the cord blood of infants with localized and systemic inflammatory pathologies and compared with that of healthy term controls. RESULTS. We identified a transcriptionally distinct population of [CD4.sup.+] T cells characterized by expression of the transcription factor promyelocytic leukemia zinc finger (PLZF). PLZ[F.sup.+][CD4.sup.+] T cells were specifically enriched in the fetal intestine, possessed an effector memory phenotype, and rapidly produced proinflammatory cytokines. Engagement of the C-type lectin CD161 on these cells inhibited TCR-dependent production of IFN-[gamma] in a fetal- specific manner. IFN-[gamma]-producing PLZ[F.sup.+][CD4.sup.+] T cells were enriched in the cord blood of infants with gastroschisis, a natural model of chronic inflammation originating from the intestine, as well as in preterm birth, suggesting these cells contribute to fetal systemic immune activation. CONCLUSION. Our work reveals a fetal-specific program of protective immunity whose dysregulation is associated with fetal and neonatal inflammatory pathologies. FUNDING. This work was supported by the UCSF Clinical and Translational Science Institute (CTSI) Pilot Award for Basic and Translational Investigators (2014908), UCSF (K12HD072222), the NIAID (K08 AI128007 and 1F31AI136336-01), a National Science Foundation (NSF) Graduate Research Fellowship (1650113), and an Academy for Medical Sciences Clinical Lecturer grant (535274).

Objective. Screening for disease using a smartphone camera is an emerging tool for conditions such as jaundice and anaemia, which are associated with a colour change (yellowing in jaundice; pallor in anaemia) of the external tissues. Based on this, we aimed to test a technique to non-invasively screen for anaemia in a population highly affected by anaemia: pregnant women in India. In this group, anaemia can have severe health consequences for both the mother and child. Approach. Over 3 years of data collection, in 486 pregnant women in India, we attempted to replicate a previously successful smartphone imaging technique to screen for anaemia. Using smartphone images of the eye and eyelid, we compared two techniques (white balancing and ambient subtraction) to control for variation in ambient lighting, and then extracted 'redness' features from images, which we used as features to predict anaemia via statistical modelling. Main results. We found that we were not able to predict anaemia with enough accuracy to be clinically useful, at 89.6% sensitivity and 26.1% specificity. We consider the hypothesis that this may be due to pigmentation on the sclera and palpebral conjunctiva. Visual judgement showed that pigmentation on the sclera, which may affect the measured colour, is more prevalent in pregnant women in India than in preschool aged children in Ghana (a population previously studied in this context). When participants with subjectively judged visible scleral pigmentation are removed, ability to screen for anaemia using the smartphone images slightly improves (93.1% sensitivity, 28.6% specificity). Significance. These findings provide evidence to reinforce that applying smartphone imaging techniques to understudied populations in the real world requires caution-a promising result in one group may not necessarily transfer to another demographic., (Creative Commons Attribution license.)