The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8+ T cells. During influenza virus infection in vivo, naive T cells enter a CD62Lintermediate state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62Lhi central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62Lhi memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.

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In order to improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, we examined the optimization of the administration of boron compounds in brain tumor animal model. We analyzed the concentration of boron atoms in intracranial C6 glioma -bearing rats using inductively coupled plasma atomic emission spectrometry. Each tumor-bearing rat received one of two different amounts of sodium borocaptate (BSH) and/or 500 mg/kg of boronophenylalanine (BPA) via intraperitoneal injection. We compared the boron concentrations of the tumor, the contralateral normal brain and the blood in rats of 3 different treatment groups (BSH alone, BPA alone and a combination of both BSH and BPA). Our results show that the tumor boron concentration increased much more than 30 microg/g by the coadministration of both compounds. Additionally, the blood boron concentration remained below 30 microg/g and the boron concentration in the normal brain was low (mean 4.7+/-1.1 microg/g). Even in comparison with the administration of BPA alone, coadministration of BPA and BSH shows an improved tumor/normal brain ratio of boron concentrations.

TF-PEG-BSH is a potent BDS for BNCT not only in terms of delivering a high concentration of (10)B into tumor tissue, but also the selective delivery of (10)B into the tumor cells.

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