ABSTRACT
Most recently, we have described the G-protein coupled receptor 83 (GPR83), which is highly expressed by CD4(+)CD25(+) regulatory T cells (Tregs) to be involved in the induction of CD4(+)Foxp3(+) Tregs in the course of an ongoing immune response. Four GPR83 isoforms have been described. Here, we have shown that GPR83 isoform-4, which differs from GPR83 isoform-1 by 20 additional aminoacids in the second cytoplasmatic loop, is predominantly expressed by Tregs. Interestingly, GPR83 isoform-4 but not GPR83 isoform-1 retrovirally transduced T cells were able to interfere with inflammatory responses in vivo. Re-analysis of GPR83 transduced T cells revealed that this in vivo acquisition of suppressive activity was associated with the induction of Treg-associated molecules including Foxp3 in GPR83 isoform-4 but not GPR83 isoform-1 transduced CD4(+) T cells under inflammatory conditions. Our results suggest that the 20 additional aminoacids within GPR83 isoform-4 are involved in Treg induction during inflammatory immune responses.
Subject(s)
Protein Isoforms/physiology , Receptors, G-Protein-Coupled/physiology , T-Lymphocytes, Regulatory/immunology , Humans , Phenotype , Protein Isoforms/genetics , Receptors, G-Protein-Coupled/geneticsABSTRACT
AIMS/HYPOTHESIS: In the NOD mouse model, attempts to show MHC class II expression by pancreatic beta cells were unsuccessful so far. We readdressed this question by analysing I-A(g7) expression in single pancreatic beta cells. METHODS: Single-cell multiplex RT PCR and single-cell immunofluorescence were used to study MHC class II expression in NOD and NOD/SCID beta cells. RESULTS: Pancreatic beta cells from NOD mice express the I-A(g7) protein as well as the corresponding mRNA. The frequency of MHC class II mRNA-expressing beta cells is drastically increased during the progression to overt diabetes. MHC class II protein is accumulated intracellularly, and invariant chain is co-expressed. Beta cells from 9- to 10-week-old NOD/SCID mice express MHC class II at the same low frequency as beta cells from 3-week-old NOD mice. CONCLUSION/INTERPRETATION: NOD beta cells express I-A(g7) and could be a direct target of autoreactive CD4+ T cells. This MHC class II expression is triggered by infiltrating lymphocytes.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Gene Expression Regulation/immunology , Histocompatibility Antigens Class II/genetics , Islets of Langerhans/immunology , Transcription, Genetic/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , Disease Progression , Mice , Mice, Inbred NOD , Mice, SCID , RNA, Messenger/genetics , Time FactorsABSTRACT
While some metabolic measurement systems measure expiratory temperature to standardize gas volumes, other systems use only an estimate. This study investigated the effect of prolonged exercise on expiratory temperature near the pneumotachometer to provide a basis for its estimation when actual measurement is unavailable. Seven active females each performed two 45-min treadmill runs at identical speeds (64.5% +/- 11.8% of VO2max) in which the pneumotachometer heater control was either set to 37 degrees C or turned off. Expired air temperatures were monitored with thermocouples at the nonrebreathing valve (VAL) and 1 cm upstream (UPS) and downstream (DNS) from the pneumotachometer screens. There were no temperature differences over time for any of the conditions, and there were no differences in the VAL or UPS temperatures between the heated and unheated conditions. DNS temperature was higher during the heated condition at all time periods (P < 0.01). Mean DNS temperatures for the heated and unheated condition were 30.2 +/- 1.0 degree C and 27.9 +/- 1.1 degrees C, respectively. We conclude that expired air temperatures near the pneumotachometer remain stable during extended steady-state exercise regardless of whether the pneumotachometer is heated or not.
