One remaining challenge in the field of colloidal semiconductor nanocrystal quantum dots is learning to control the degree of functionalization or "valence" per nanocrystal. Current quantum dot surface modification strategies rely heavily on ligand exchange, which consists of replacing the nanocrystal's native ligands with carboxylate-or amine-terminated thiols, usually added in excess. Removing the nanocrystal's native ligands can cause etching and introduce surface defects, thus affecting the nanocrystal's optical properties. More importantly, ligand exchange methods fail to control the extent of surface modification or number of functional groups introduced per nanocrystal. Here, we report a fundamentally new surface ligand modification or "doping" approach aimed at controlling the degree of functionalization or valence per nanocrystal while retaining the nanocrystal's original colloidal and photostability. We show that surface-doped quantum dots capped with chemically active native ligands can be prepared directly from a mixture of ligands with similar chain lengths. Specifically, vinyl and azide-terminated carboxylic acid ligands survive the high temperatures needed for nanocrystal synthesis. The ratio between chemically active and inactive-terminated ligands is maintained on the nanocrystal surface, allowing to control the extent of surface modification by straightforward organic reactions. Using a combination of optical and structural characterization tools, including IR and 2D NMR, we show that carboxylates bind in a bidentate chelate fashion, forming a single monolayer of ligands that are perpendicular to the nanocrystal surface. Moreover, we show that mixtures of ligands with similar chain lengths homogeneously distribute themselves on the nanocrystal surface. We expect this new surface doping approach will be widely applicable to other nanocrystal compositions and morphologies, as well as to many specific applications in biology and materials science. ABSTRACT: One remaining challenge in the field of colloidal semiconductor nanocrystal quantum dots is learning to control the degree of functionalization or "valence" per nanocrystal. Current quantum dot surface modification strategies rely heavily on ligand exchange, which consists of replacing the nanocrystal's native ligands with carboxylate-or amine-terminated thiols, usually added in excess. Removing the nanocrystal's native ligands can cause etching and introduce surface defects, thus affecting the nanocrystal's optical properties. More importantly, ligand exchange methods fail to control the extent of surface modification or number of functional groups introduced per nanocrystal. Here, we report a fundamentally new surface ligand modification or "doping" approach aimed at controlling the degree of functionalization or valence per nanocrystal while retaining the nanocrystal's original colloidal and photostability. We show that surface-doped quantum dots capped with chemically active native ligands can be prepared directly from a mixture of...

Highlights d Both p35 and p40 subunits of IL-12 are required to differentiate IFNg-producing T cells d p35 and p40 produced by two different cells can collaborate to drive T cell responses d The two-cell IL-12 activity requires hematopoietic p40 but can use stromal p35 d Two-cell IL-12 activity is useful for controlling pathogen dissemination in vivo

Peripheral T cells express a diverse repertoire of antigen-specific receptors, which together protect against the full range of pathogens. In this context, the total repertoire of memory T cells which are maintained by trophic signals, long after pathogen clearance, is critical. Since these trophic factors include cytokines and self-peptide-MHC, both of which are available from endogenous antigen-presenting cells (APC), we hypothesized that enhancing APC numbers in vivo can be a viable strategy to amplify the population of memory T cells. We evaluated this by acutely treating intact mice with FMS-like tyrosine kinase 3 ligand (Flt3l), which promotes expansion of APCs. Here we report that this treatment allowed for, an expansion of effector-memory CD4+ and CD8+ T cells as well as an increase in their expression of KLRG1 and CD25. In the lymph nodes and spleen, the expansion was limited to a specific CD8 (CD44-low but CD62L−) subset. Functionally, this subset is distinct from naïve T cells and could produce significant amounts of effector cytokines upon restimulation. Taken together, these data suggest that the administration of Flt3L can impact both APC turnover as well as a corresponding flux of specific subsets of CD8+ T cells in an intact peripheral immune compartment.

Cytokines are typically single gene products that potently modify immune responses. The IL-12 family is an exception to this paradigm as these cytokines are heterodimers. In the case of IL-12, the subunits, IL-12p40 and IL-12p35 are encoded by two unlinked genes. However, it is canonical that activated myeloid cells co-express both these subunits simultaneously and secrete a fully active heterodimer of IL-12 which then drives IFNγ production by innate and adaptive cells. Using a chimeric mouse model, we identified a novel method of formation for generating functional IL-12 activity in vivo involving IL-12p40 monomers originating from hematopoietic cells which extracellularly associate with IL-12p35 from other non-hematopoietic cells. In the context of a parasitic challenge, we found that this two-cell mechanism of IL-12 formation was sufficient to drive T cell differentiation in local sites, distal to the initial infection, and thereby regulate systemic dissemination of the pathogen. Accordingly, we identify a new collaboration between hematopoietic and non-hematopoietic cells to produce functional IL-12 through the regulated release of individual subunits as a systemic alert system to prepare host tissues for potential pathogen arrival.