Donor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease.

The adoptive transfer of regulatory T cells is a promising strategy to prevent graft-versus-host disease after allogeneic bone marrow transplantation. Here, we use a major histocompatibility complex-mismatched mouse model to follow the fate of in vitro expanded donor regulatory T cells upon migration to target organs. Employing comprehensive gene expression and repertoire profiling, we show that they retain their suppressive function and plasticity after transfer. Upon entering non-lymphoid tissues, donor regulatory T cells acquire organ-specific gene expression profiles resembling tissue-resident cells and activate hallmark suppressive and cytotoxic pathways, most evidently in the colon, when co-transplanted with graft-versus-host disease-inducing conventional T cells. Dominant T cell receptor clonotypes overlap between organs and across recipients and their relative abundance correlates with protection efficacy. Thus, this study reveals donor regulatory T cell selection and adaptation mechanisms in target organs and highlights protective features of Treg to guide the development of improved graft-versus-host disease prevention strategies.

Strain specific differences in vitamin D3 response: impact on gut homeostasis.

Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells in vitro. Weak regulatory effects were detected on murine T cells. By trend, the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 suppressed IFN, GM-CSF and IL-10 cytokine secretion in T cells of C57BL/6 but not BALB/c mice, respectively. Using different vitamin D3-fortified diets, we found a tissue-specific enrichment of mainly CD11b+ myeloid cells but not T cells in both mouse strains e.g. in spleen and Peyer's Patches. Mucin Reg3γ and Batf expression, as well as important proteins for gut homeostasis, were significantly suppressed in the small intestine of C57BL76 but not BALB/c mice fed with a high-vitamin D3 containing diet. Differences between both mouse stains were not completely explained by differences in vitamin D3 receptor expression which was strongly expressed in epithelial cells of both strains. Finally, we analyzed gut microbiome and again an impact of vitamin D3 was detected in C57BL76 but not BALB/c. Our data suggest strain-specific differences in vitamin D3 responsiveness under steady state conditions which may have important implications when choosing a murine disease model to study vitamin D3 effects.

Health-related quality of life and IGF-1 in GH-deficient adult patients on GH replacement therapy: analysis of the German KIMS data and the Study of Health in Pomerania.

OBJECTIVE: To analyse 12-month response to GH treatment in a single-country cohort of hypopituitary adult patients with GH deficiency (GHD) in regards to health-related quality of life (HRQoL) and insulin-like growth factor-1 (IGF-1) compared with values from general population sample. Moreover, association between the response in HRQoL and the IGF-1 values in patients and in the background population was investigated. DESIGN: HRQoL was assessed by quality of life assessment of GH deficiency in adults (QoL-AGHDA) in 651 patients retrieved from the German KIMS (Pfizer International Metabolic Database) before and after 12 months of GH replacement and in a sample drawn from a cross-sectional study in Germany (n=2734). IGF-1 was measured in KIMS patients and in the population-based study with the same assay technique. RESULTS: In KIMS patients, mean QoL-AGHDA scores before GH replacement were 9.2+/-6.8 (8.7+/-6.8) in women (men) and in the general population sample 4.5+/-5.3 (4.3+/-5.0) in women (men). Mean differences in QoL-AGHDA scores were statistically significant for all age categories (P<0.05). The mean IGF-1 SDS of KIMS patients before GH replacement was -1.1+/-1.4 (-0.8+/-1.4) in women (men). After GH replacement, a significant increase of IGF-1 concentration and a significant decrease of QoL-AGHDA scores near to age- and gender-specific population-based values were observed. CONCLUSIONS: This study confirms an improvement in HRQoL and an increase of IGF-1 SDS in GH-replaced adults, which approximated the values of general population. However, there was no association between IGF-1 values and HRQoL assessment as one of the important treatment outcomes.