Search

Summary Complications after vaccination, lack of vaccines against certain infections, and the emergence of antibiotic-resistant microorganisms point to the need for alternative ways of protection and treatment of infectious diseases. Here, we proposed a therapeutic approach to control salmonellosis based on adoptive cell therapy. We showed that the T cell receptor (TCR) repertoire of salmonella-specific memory cells contains 20% of TCR variants with the dominant-active α-chain. Transduction of intact T lymphocytes with the dominant salmonella-specific TCRα led to their enhanced in vitro proliferation in response to salmonella. Adoptive transfer of transduced T cells resulted in a significant decrease in bacterial loads in mice infected with salmonella before or after the adoptive transfer. We demonstrated that adoptive immunotherapy based on T cells, transduced with dominant-specific TCRα could be successfully applied for treatment and prevention of infectious diseases and represent a useful addition to vaccination and existing therapeutic strategies., Graphical Abstract, Highlights • A regular TCR repertoire of memory T cells contains alpha-chain-centric TCRs • Dominant-active TCRα, paired with random TCRβ, recognizes specific microbial antigens • Adoptive immunotherapy could be applied for treatment of infections, Immunology; Microbiology

Projection neurons of the developing cerebral cortex are generated in the cerebral ventricular zone and subsequently move to the developing cortical plate via radial migration. Conversely, most inhibitory interneurons originate in the ganglionic eminences and enter the developing cortical plate by tangential migration. Using immunohistochemical analysis together with tracer labeling experiments in organotypic brain slices, we show that a portion of cortical projection neurons migrates tangentially over long distances. Lineage analysis revealed that these neurons are derived from Emx1+ cortical progenitors and express the transcription factor Satb2 but do not express GABA or Olig1. In vitro and in vivo analysis of reeler mutant brains demonstrated that although reeler mutation does not influence tangential migration of interneurons, it affects the tangential migration of cortical projection neurons.

The cerebral cortex is a tissue with a high degree of neuronal diversity. It consists of six cell layers with a unique set of neuronal subtypes. A crucial step in the process of cortical differentiation is the transition from a mitotically active neuroblast to a postmitotic young neuron. To identify genes involved in the control of this transition, we applied a novel method of cDNA subtraction based on mirror-orientation selection. One of the genes we have identified in our screening proved to be a mouse homolog of the human putative transcription factor LAF4. We identified alternatively spliced forms of mouse Laf4 that encode several forms of putative protein with potentially different transactivation functions. Two forms are expressed mainly during embryogenesis, whereas the other forms are expressed mainly in adults. We have found that Laf4 transcription becomes very quickly upregulated as soon as young cortical neurons leave the ventricular zone (VZ), the cortical-proliferative compartment. This coincides with the initial steps of cortical differentiation. Laf4 becomes downregulated in postnatal cortex, indicating its involvement in the transcriptional regulation of the early steps of cortical differentiation. We have also examined Laf4 expression in the brains of Sey and reeler mutants. Laf4 was downregulated in the lateroventral part of the cerebral cortex and completely lost in the piriform cortex of the Sey mutant embryos. We also compared its expression during central nervous system development with that of its closest homolog, Fmr2, a gene implicated in mental retardation in humans.