ABSTRACT
How follicular T-helper (Tfh) cells develop is incompletely understood. We find that, upon antigen exposure in vivo, both naïve and antigen-experienced T cells sequentially upregulate CXCR5 and Bcl6 within the first 24 h, relocate to the T-B border, and give rise to phenotypic Bcl6(+)CXCR5(+) Tfh cells before the first cell division. CXCR5 upregulation is more dependent on ICOS costimulation than that of Bcl6, and early Bcl6 induction requires T-cell expression of CXCR5 and, presumably, relocation toward the follicle. This early and rapid upregulation of CXCR5 and Bcl6 depends on IL-6 produced by radiation-resistant cells. These results suggest that a Bcl6(hi)CXCR5(hi) phenotype does not automatically define a Tfh lineage but might reflect a state of antigen exposure and non-commitment to terminal effector fates and that niches in the T-B border and/or the follicle are important for optimal Bcl6 induction and maintenance.
Subject(s)
Animals , Mice , CD40 Ligand , Metabolism , Cell Differentiation , Physiology , DNA-Binding Proteins , Metabolism , Inducible T-Cell Co-Stimulator Protein , Metabolism , Interleukin-6 , Metabolism , Proto-Oncogene Proteins c-bcl-6 , Receptors, CXCR5 , Metabolism , T-Lymphocytes, Helper-Inducer , MetabolismABSTRACT
Liver blood flow was measured in normal & CCl4-intoxicated mice & rats, using the electrolysis-generated hydrogen gas method. The results showed that the intramuscular injection of 6-15/kg of ISM increased significantly the liver blood flow in normal mice & rats. In acute or chronic CCl4-intoxicated mice & rats, the liver blood was decreased but the blood flow was restored the normal level by the ISM. In addition, the protective effect against liver injury was also observed by the histological examination & electron micrographs.The above results suggest that the protective effect of ISM against CCl4-induced liver injury seems to be through increasing the liver blood flow, improving liver's microcirculation & preventing or mitgating the denaturing or necrosis of liver cells.