Human thymocytes, unlike mouse thymocytes, express major histocompatibility complex (MHC) class II molecules on their surface, especially during the fetal and perinatal stages. Based on this observation, we previously identified a novel developmental pathway for the generation of CD4+ T cells via interactions between MHC class II–expressing thymocytes (thymocyte–thymocyte [T–T] interactions) with a transgenic mouse system. However, the developmental dissection of this T–T interaction in humans has not been possible because of the lack of known cellular molecules specific for T–T CD4+ T cells. We show that promyelocytic leukemia zinc finger protein (PLZF) is a useful marker for the identification of T–T CD4+ T cells. With this analysis, we determined that a substantial number of fetal thymocytes and splenocytes express PLZF and acquire innate characteristics during their development in humans. Although these characteristics are quite similar to invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have a diverse T cell receptor repertoire and are restricted by MHC class II molecules. These findings define a novel human CD4+ T cell subset that develops via an MHC class II–dependent T–T interaction.

ZnO nanorods were grown on SiO2/Si substrates by a sol-gel method at low temperatures of around T=95 °C. The diameters and the lengths of ZnO nanorods increased at high concentrations of zinc nitrate hexahydrate and methenamine solution. Current–voltage characteristics of the ZnO nanorods network followed a typical nonlinear behavior with significant photoresponse below λ<400 nm in air, and the conductance was enhanced in vacuum with negligible photoresponse. In photoluminescence (PL) and photocurrent (PC) spectra, the PL peak (λpeak=380 nm and 3.26 eV) did not match the PC edge (λedge=400 nm and 3.1 eV), indicating the nondirect band-gap transition in photocurrent. The origin of the photocurrent was discussed from the point of the influence of the desorption of adsorbed water molecules on the surface or inside the ZnO nanorods.

We have recently shown that MHC class II-dependent thymocyte–thymocyte (T-T) interaction successfully generates CD4+ T cells (T-T CD4+ T cells), and that T-T CD4+ T cells expressing promyelocytic leukemia zinc finger protein (PLZF) show an innate property both in mice and humans. In this article, we report that the thymic T-T interaction is essential for the conversion of CD8+ T cells into innate phenotype in the physiological condition. CD8+ T cells developed in the presence of PLZF+ CD4+ T cells showed marked upregulation of eomesodermin (Eomes), activation/memory phenotype, and rapid production of IFN-γ on ex vivo stimulation. Their development was highly dependent on the PLZF expression in T-T CD4+ T cells and the IL-4 secreted by PLZF+ T-T CD4+ T cells. The same events may take place in humans, as a substantial number of Eomes expressing innate CD8+ T cells were found in human fetal thymi and spleens. It suggests that PLZF+ T-T CD4+ T cells in combination with Eomes+ CD8+ T cells might actively participate in the innate immune response against various pathogens, particularly in human perinatal period.

Administration of an ICAM-1–specific antibody arrests dendritic cells in a semi-immature state and facilitates antigen-specific T cell tolerance to islet allografts in humanized mice and Rhesus monkeys.