We recently reported that the number of γδ T cells was increased after infection with Escherichia coli in C3H/HeN mice. We here showed that an i.p. injection with native lipid A derived from E. coli induced an increase of γδ T cells in the peritoneal cavity of LPS-responsive C3H/HeN mice and, albeit to a lesser degree, also in LPS-hyporesponsive C3H/HeJ mice. The purified γδ T cells from C3H/HeN and C3H/HeJ mice expressed a canonical TCR repertoire encoded by Vγ6-Jγ1/Vδ1-Dδ2-Jδ2 gene segments and proliferated in response to the native lipid A derived from E. coli in a TCR-independent manner. The lipid A-reactive γδ T cells bearing canonical Vγ6/Vδ1 expressed Toll-like receptor (TLR) 2 mRNA, while TLR4 mRNA was undetectable. Treatment with a TLR2 anti-sense oligonucleotide resulted in hyporesponsiveness of the γδ T cells to the native lipid A. TLR2-deficient mice showed an impaired increase of the γδ T cells following injection of native lipid A. These results suggest that TLR2 is involved in the activation of canonical Vγ6/Vδ1 T cells by native E. coli lipid A.

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Overall, the CLIP and the JIS scoring systems proved to be suitable for patients in Japan with HCC. The CLIP staging systems proved to be more suitable before 1991. In contrast, the JIS system was the most suitable after 1990, when early detection and early treatment of HCC became common. The JIS system is, therefore, the appropriate system in this era of early detection and treatment of HCC.

We cloned the 5' upstream region of IL-15 genomic DNA and examined promoter activity in macrophages stimulated with lipopolysaccharide(LPS). The 1.2 kilobase (kb) fragment of the 5' upstream region contained binding elements for LPS-inducible transcription factors such as NFIL-6 or NF-kappaB. Determined by luciferase assay following transient transfection in the J774A.1 macrophage cell line, the 1.2 kb of the 5' upstream region exhibited high promoter activity in response to LPS, while promoter activity was significantly reduced by the 5' deletion of 313 base pairs containing the NF-kappaB binding motif. Nuclear protein prepared from LPS-stimulated macrophages formed a complex with the NF-kappaB binding sequence of the IL-15 promoter. Taken together, the binding of nuclear protein to the NF-kappaB binding site is required for transcriptional activation of the IL-15 gene in LPS-stimulated macrophages.