SUMMARY Although pregnancy confers unique susceptibility to infection, the pregnancy-associated immune defects that erode host defense remain largely undefined. Herein, we demonstrate that expansion of immune-suppressive Foxp3+ regulatory T cells (Tregs) which occurs physiologically during pregnancy or when experimentally induced in transgenic mice each caused enhanced susceptibility to prenatal pathogens including Listeria and Salmonella species. Reciprocally, infection susceptibility was uniformly reduced with Treg-ablation. Importantly however, the sustained expansion of maternal Tregs was essential for maintaining immune tolerance to the developing fetus because even partial transient ablation of Foxp3-expressing cells fractured maternal tolerance to fetal antigen and triggered fetal resorption. Interestingly, Foxp3 cell-intrinsic defects in the immune suppressive cytokine IL-10 alone were sufficient to override Treg-mediated infection susceptibility, while IL-10 was non-essential for sustaining pregnancy. Thus, maternal Treg expansion required for sustaining pregnancy creates naturally occurring holes in host defense that confers prenatal infection susceptibility.

T cell activation is controlled by incompletely defined opposing stimulation and suppression signals that together sustain the balance between optimal host defense against infection and peripheral tolerance. Herein, we explored the impacts of Foxp3+ regulatory T cell (Treg) suppression in priming antigen-specific T cell activation under non-infection and infection conditions. We find the transient ablation of Foxp3+ Tregs unleashes the robust expansion and activation of peptide stimulated CD8+ T cells that provide protection against Listeria monocytogenes (Lm) infection in an antigen-specific fashion. By contrast, Treg-ablation had non-significant impacts on the CD8+ T cell response primed by infection with recombinant Lm. Similarly, non-recombinant Lm administered with peptide stimulated the expansion and activation of CD8+ T cells that paralleled the response primed by Treg-ablation. Interestingly, these adjuvant properties of Lm did not require CD8+ T cell stimulation by IL-12 produced in response to infection, but instead were associated with sharp reductions in Foxp3+ Treg suppressive potency. Therefore, Foxp3+ Tregs impose critical barriers that when overcome naturally during infection or artificially with ablation allows the priming of protective antigen-specific CD8+ T cells.

Summary Typhoid fever is a persistent infection caused by host‐adapted Salmonella strains adept at circumventing immune‐mediated host defences. Given the importance of T cells in protection, the culling of activated CD4+ T cells after primary infection has been proposed as a potential immune evasion strategy used by this pathogen. We demonstrate that the purging of activated antigen‐specific CD4+ T cells after virulent Salmonella infection requires SPI‐2 encoded virulence determinants, and is not restricted only to cells with specificity to Salmonella‐expressed antigens, but extends to CD4+ T cells primed to expand by co‐infection with recombinant Listeria monocytogenes. Unexpectedly, however, the loss of activated CD4+ T cells during Salmonella infection demonstrated using a monoclonal population of adoptively transferred CD4+ T cells was not reproduced among the endogenous repertoire of antigen‐specific CD4+ T cells identified with MHC class II tetramer. Analysis of T‐cell receptor variable segment usage revealed the selective loss and reciprocal enrichment of defined CD4+ T‐cell subsets after Salmonella co‐infection that is associated with the purging of antigen‐specific cells with the highest intensity of tetramer staining. Hence, virulent Salmonella triggers the selective culling of high avidity activated CD4+ T‐cell subsets, which re‐shapes the repertoire of antigen‐specific T cells that persist later after infection.

Objectives In 2009 the IOM revised prenatal weight gain guidelines. The primary purpose of this pilot study was to assess if provider education and use of prenatal weight gain charts to track weight gain and counsel patients was associated with better patient and provider knowledge and communication about the guidelines. Methods A prospective non-randomized study conducted in four OB practices (two control, two intervention). Data sources included provider surveys (n = 16 intervention, 21 control), patient surveys (n = 332), and medical records. Intervention clinics received provider education on the IOM guidelines and used patient education materials and prenatal weight gain charts to track weight gain and as a counseling tool. Comparison clinics received no education and did not use the charts or patient education information. Results More patients at intervention clinics (92.3%) reported that a provider gave them advice about weight gain, compared to patients from comparison clinics (66.4%) (p < 0.001). Intervention patients were also more likely to report satisfaction discussions with their provider about weight gain (83.1 vs. 64.3%, p = 0.007). Intervention clinic patients were more likely to have knowledge of the guidelines indicated by 72.3% reporting a target weight gain amount within the guidelines versus 50.4% of comparison patients (p < 0.001). Conclusion Provider education and use of weight gain charts resulted in higher patient reported communication about weight gain from their provider, higher patient satisfaction with those discussions, and better knowledge of the appropriate target weight gain goals.

Women with CF who are homozygous for the ΔF508 mutation have an increased risk of having a pregnancy complicated by diabetes.