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Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown. Deletion of Btla demonstrated BTLA regulates CD5 expression. Loss of BTLA signals, but not signalling by its ligand, HVEM, leads to increased CD5 expression. Higher CD5 expression set during thymic selection is associated with increased self-recognition, suggesting that BTLA might be needed early to establish self-tolerance. We found that BTLA and PD-1 were needed post-thymic selection in recent thymic emigrants (RTE). RTE lacking BTLA caused a CD4 T cell and MHC class II dependent multi-organ autoimmune disease. Together, our findings identify a negative regulatory pathway between two constitutively expressed co-inhibitors, calibrating their expression. Expression of constitutive and induced co-inhibitory receptors is needed early to establish tolerance in the periphery for RTE.

Denne studien undersøkjer barnehagelærarars forteljingar om språkarbeid med fleirspråklege barn i barnehagen. Målet med studien var å få innsikt i barnehagelærars oppfatningar som dei byggjer praksisen med fleirspråklege barn i barnehagen på. Fire fokusgruppeintervju med totalt 20 barnehagelærarar blei gjennomførte. Den narrative analysen identifiserte fire sentrale tolkingsrepertoar for barnehagelæraranes oppfatningar av fleirspråkleg praksis: det ressursprega, det kompensatoriske, det monospråklege og det profesjonelle avmaktsrepertoaret. Tolkingsrepertoara kom til syne i alle fire intervjua, og dette tyder på eit mønster i oppfatningane. Tolkingsrepertoara var ikkje gjensidig utelukkande, til dømes kunne barnehagelærar både gi uttrykk for å oppfatte fleirspråklegheit som ressurs og samtidig kjenne avmakt i si eiga rolle. Likeins blei norskspråkleg utvikling trekt fram som målsetting for barnehagens språkarbeid samtidig som deltakarane fortalde om spontane transspråkingsaktivitetar. Dette tyder på ein variert og kompleks språkpraksis bygd på både formell og erfaringsbasert kompetanse og personlege oppfatningar. Funna gir innblikk i korleis barnehagelærarar forstår sin eigen og barnas posisjon i ein fleirspråkleg barnehagekontekst og har implikasjonar for utvikling av ein ressursbasert fleirspråkleg pedagogisk praksis. ENGLISH ABSTRACT Resource and Deficiency: Teachers’ Views on Complex Multilingual Practices in Early Childhood Education and Care This study explores teachers’ experiences of multilingual practices in early childhood education and care (ECEC). The purpose was to gain insight into the underlying assumptions that shape ECEC teachers’ multilingual practices. Data were collected through four focus group interviews with 20 teachers. The analysis of the ECEC teachers’ narratives identified four emerging interpretative repertoires: resource-based, compensatory, monolingual, and feelings of professional powerlessness. All four interpretative repertoires appeared in all the interviews, which suggests a pattern of views. The interpretative repertoires were not mutually exclusive. One participant could, for instance, explicitly view multilingualism as a resource while simultaneously expressing feelings of powerlessness regarding how to practice multilingual didactics. Similarly, monolingual Norwegian development was identified as the objective of planned activities while teachers described spontaneous translingual activities. These findings indicate varied and complex linguistic practices built on formal and experience-based competencies and personal beliefs and provide insight into ECEC teachers’ understandings of their own and the children’s positions within a complex multilingual ECEC context. The results have implications for further research- based development of multilingual practices.

Colitis is characterized by an exacerbated intestinal immune response, but the genetic and other mechanisms regulating immune activation remain incompletely understood. In order to identify new pathways leading to colitis, we sought to identify genes with increased expression in the colons of patients that also are near loci identified by genome wide association studies (GWAS) associated with IBD risk. One such SNP, rs9557195 was of particular interest because it is within an intron of G-protein-coupled receptor (GPR) 183, known to be important for lymphocyte migration. Furthermore, this SNP is in close proximity to the gene encoding another G-protein coupled receptor, GPR18. Analyzing publicly available datasets, we found transcripts of GPR183 and GPR18 to be increased in colon biopsies from ulcerative colitis and Crohn’s disease patients, and GPR183 was even more increased in patients resistant to TNF treatment. Expression of both genes also was increased in mouse models of colitis. Therefore, our aim was to understand if increased expression of these GPRs in the intestine is related to disease severity in colitis models. Here we investigated the role of these receptors in the T cell transfer model and the dextran sulfate sodium model. In the T cell transfer model, GPR183 expression on donor T cells, as well as on other cell types in the Rag-/- recipients, was not essential for severe colitis induction. Furthermore, deficiency in Rag-/- mice for the enzyme that synthesizes a cholesterol metabolite that is a major ligand for GPR183 also did not affect disease. Similarly, lack of GPR18 expression in T cells or other cell types did not affect colitis pathogenesis in the T cell transfer or in the dextran sulfate sodium model. Therefore, despite increased expression of transcripts for these genes in the intestine during inflammation in humans and mice, they are not required for disease severity in mouse models of colitis induced by chemical injury or T cell cytokines, perhaps due to redundancy in mechanisms important for homing and survival of lymphocytes to the inflamed intestine.

The B and T lymphocyte attenuator (BTLA) is an Ig super family member that binds to the herpes virus entry mediator (HVEM), a TNF receptor super family (TNFRSF) member. Engagement of BTLA by HVEM triggers inhibitory signals, although recent evidence indicates that BTLA also may act as an activating ligand for HVEM. In this study, we reveal a novel role for the BTLA-HVEM pathway in promoting the survival of activated CD8(+) T cells in the response to an oral microbial infection. Our data show that both BTLA- and HVEM-deficient mice infected with Listeria monocytogenes had significantly reduced numbers of primary effector and memory CD8(+) T cells, despite normal proliferation and expansion compared to controls. In addition, blockade of the BTLA-HVEM interaction early in the response led to significantly reduced numbers of antigen-specific CD8(+) T cells. HVEM expression on the CD8(+) T cells as well as BTLA expression on a cell type other than CD8(+) T lymphocytes, was required. Collectively, our data demonstrate that the function of the BTLA-HVEM pathway is not limited to inhibitory signaling in T lymphocytes, and instead, that BTLA can provide crucial, HVEM-dependent signals that promote survival of antigen activated CD8(+) T cell during bacterial infection.