Infant B cell memory differentiation and early gut bacterial colonization.

Germ-free animal models have demonstrated that commensal bacterial colonization of the intestine induces B cell differentiation and activation. Whether colonization with particular bacterial species or groups is associated with B cell development during early childhood is not known. In a prospective newborn/infant cohort including 65 Swedish children, we examined the numbers and proportions of CD20(+), CD5(+), and CD27(+) B cells in blood samples obtained at several time points during the first 3 y of life using flow cytometry. Fecal samples were collected and cultured quantitatively for major facultative and anaerobic bacteria at 1, 2, 4, and 8 wk of life. We found that the numbers of CD20(+) B cells and CD5(+)CD20(+) B cells reached their highest levels at 4 mo, whereas CD20(+) B cells expressing the memory marker CD27 were most numerous at 18 and 36 mo of age. Using multivariate analysis, we show that early colonization with Escherichia coli and bifidobacteria were associated with higher numbers of CD20(+) B cells that expressed the memory marker CD27 at 4 and 18 mo of age. In contrast, we were unable to demonstrate any relation between bacterial colonization pattern and numbers of CD20(+) or CD5(+)CD20(+) B cells. These results suggest that the intestinal bacterial colonization pattern may affect the B cell maturation also in humans, and that an early gut microbiota including E. coli and bifidobacteria might promote this maturation.

Improved Glycemic Control Observed in Children with Type 1 Diabetes Following the Introduction of Smart Insulin Pens: A Real-World Study.

INTRODUCTION: Many challenges are associated with optimizing glycemic control in pediatric patients with type 1 diabetes (T1D); combining data from smart insulin pens and continuous glucose monitoring (CGM) could mitigate some of these obstacles. METHODS: This one-arm, prospective, observational study investigated the effects of introducing a smart pen on glycemic control in pediatric patients with T1D who were using CGM. Children and adolescents with T1D who had been prescribed a smart pen for basal and/or bolus insulin injections were enrolled from three clinics in Sweden. Outcomes compared between baseline and follow-up (≥ 12 months) included: mean numbers of daily (over 24 h) and nocturnal hypoglycemic or hyperglycemic events; time above range (TAR; > 180 mg/dL); time below range (TBR; level 1: 54 to < 70 mg/dL; level 2: < 54 mg/dL); time in range (TIR; 70-180 mg/dL); and missed bolus-dose (MBD) meals. RESULTS: Overall, 39 patients were included. Mean numbers of daily hypoglycemic events (- 31.4%; p = 0.00035) and nocturnal hypoglycemic events (- 24.4%; p = 0.043) were significantly reduced from baseline to follow-up. Mean daily TBR level 2 was reduced from 2.82% at baseline to 2.18% at follow-up (- 0.64 percentage points; p = 0.025). There were no statistically significant changes in number of daily hyperglycemic events, MBD meals, TIR, TAR, or TBR level 1. CONCLUSIONS: Introducing smart insulin pens was associated with a reduced number of hypoglycemic events and decreases in TBR level 2, demonstrating a potential benefit for glycemic control in pediatric patients.

Stronger T cell immunogenicity of ovalbumin expressed intracellularly in Gram-negative than in Gram-positive bacteria.

This study aimed to clarify whether Gram-positive (G+) and Gram-negative (G-) bacteria affect antigen-presenting cells differently and thereby influence the immunogenicity of proteins they express. Lactobacilli, lactococci and Escherichia coli strains were transformed with plasmids conferring intracellular ovalbumin (OVA) production. Murine splenic antigen presenting cells (APCs) were pulsed with washed and UV-inactivated OVA-producing bacteria, control bacteria, or soluble OVA. The ability of the APCs to activate OVA-specific DO11.10 CD4(+) T cells was assessed by measurments of T cell proliferation and cytokine (IFN-γ, IL-13, IL-17, IL-10) production. OVA expressed within E. coli was strongly immunogenic, since 500 times higher concentrations of soluble OVA were needed to achieve a similar level of OVA-specific T cell proliferation. Furthermore, T cells responding to soluble OVA produced mainly IL-13, while T cells responding to E. coli-expressed OVA produced high levels of both IFN-γ and IL-13. Compared to E. coli, G+ lactobacilli and lactococci were poor inducers of OVA-specific T cell proliferation and cytokine production, despite efficient intracellular expression and production of OVA and despite being efficiently phagocytosed. These results demonstrate a pronounced difference in immunogenicity of intracellular antigens in G+ and G- bacteria and may be relevant for the use of bacterial carriers in vaccine development.