ABSTRACT
Interleukin (IL)-7 is a factor essential for mouse and human thymopoiesis. Mouse thymocytes have altered sensitivities to IL-7 at different developmental stages. CD4/CD8 double positive (DP) mouse thymocytes are shielded from the influence of IL-7 because of loss of CD127 (IL-7Ralpha). In this study, we assessed IL-7 receptor expression and IL-7 signaling in human thymocytes. We found human DP cells to be severely limited in their ability to phosphorylate STAT-5 in response to IL-7. The relative expression levels of the IL-7-inducible proteins Bcl-2 and Mcl-1 were also lower in human DP cells, consistent with a stage-specific decrease in IL-7 responsiveness. IL-7 responses were restored in a subset of cells that matured past the DP stage. Unlike the regulation of IL-7 signaling in mouse thymocytes, loss of IL-7 signaling in human DP cells was not due to absence of CD127, but instead correlated with downregulation of CD132 (common gamma chain).
Subject(s)
Interleukin Receptor Common gamma Subunit/metabolism , Interleukin-7/pharmacology , Precursor Cells, T-Lymphoid/drug effects , Receptors, Interleukin-7/metabolism , Animals , CD4 Antigens/biosynthesis , CD8 Antigens/biosynthesis , Cell Differentiation , Cells, Cultured , Child, Preschool , Humans , Infant , Infant, Newborn , Interleukin Receptor Common gamma Subunit/genetics , Interleukin Receptor Common gamma Subunit/immunology , Interleukin-7/immunology , Mice , Precursor Cells, T-Lymphoid/cytology , Precursor Cells, T-Lymphoid/immunology , Precursor Cells, T-Lymphoid/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Receptors, Interleukin-7/genetics , Receptors, Interleukin-7/immunology , STAT5 Transcription Factor/genetics , STAT5 Transcription Factor/metabolism , Signal Transduction/drug effects , Signal Transduction/immunology , Thymus Gland/cytology , Thymus Gland/immunologyABSTRACT
BACKGROUND: Recently, it has been suggested that Helicobacter pylori might be a cause of some cases of infantile hypertrophic pyloric stenosis (IHPS) in infancy on the basis of its epidemiologic and clinical features. We performed this study to evaluate the possible relationship between IHPS and H. pylori. DESIGN: In consecutive infants with IHPS, we performed upper gastrointestinal endoscopy with biopsy before pyloromyotomy. The endoscopic appearance of the pylorus was noted to validate endoscopic features of IHPS. RESULTS: Sixteen infants, 15 male, 14 white, mean age 42 days, range 21 to 104 days, were studied. The index case had chronic active gastritis on biopsy with organisms suspicious for H. pylori. Four others had chronic active gastritis, six more had focal or mild chronic gastritis, five were normal, and none had H. pylori on histology or immune histochemical staining in selected cases. All patients had negative rapid urease test. Most common endoscopic findings of IHPS were thickened prominent asymmetric pyloric folds and pin-hole pylorus that could not be intubated by the pediatric endoscope. CONCLUSION: H. pylori was not specifically identified in our patients with IHPS. The presence of H. pylori-like organisms in the gastric mucosa in our index case and finding of chronic active gastritis in several others may indicate the possibility of an acquired infectious etiology for IHPS.
