CHARACTERIZATION OF SPLENIC LYMPHOID CELLS IN FETAL AND NEWBORN MICE

In order to clarify the cellular events that precede the onset of immunological competence in the mouse, we have characterized and quantitated the lymphoid cells of the spleen as a function of age. Our results show that T cells and B cells both appeared in the spleens of Swiss-L mice as early as the 15th-16th day of gestation. Antigen-binding cells specific for each of three different antigens were also first detected during this same 24 h interval. The B cells and three varieties of antigen-binding cells increased in number rapidly and in parallel until about 1 wk after birth. The T cells, which were more numerous than B cells at first, increased in number somewhat more slowly. Coincident with the onset of response to antigen, there was a further increase in B cell numbers and a decrease in the T cell to B cell ratio. The capacity to respond to antigen by cellular proliferation and synthesis of antibody did not arise until about 2 wk after birth although there were no quantitative changes in the total numbers of T cells, B cells, and antigen-binding cells between 1 and 2 wk of age. Some qualitative change, such as the functional maturation of an antigen-reactive cell, may be required during this interval for the onset of this immunological response. Although the numbers of antigen-binding cells present in fetuses and young animals were smaller than in adults, we have as yet been unable to detect any restriction in the variety of specificities that can be expressed in fetuses, either in the kinds of antigens bound or in the range of avidities with which a single antigen is bound

The distribution of NCAM in the chick hindlimb during axon outgrowth and synaptogenesis

We have determined the distribution and form of the neural cell adhesion molecule (NCAM) in the chick hindlimb from initial axon outgrowth (stage ) until 3 days posthatching by immunohistological staining and sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots. Axons stained intensely for NCAM at all ages, whereas non-neuronal limb components exhibited dynamic changes in staining. Mesenchymal cells in the sclerotome adjacent to the neural tube developed NCAM immunoreactivity in an anterior-posterior sequence which correlated with the sequence of axonal outgrowth. Low to moderate amounts of NCAM were detected within and surrounding presumptive nerve pathways, consistent with a permissive role for NCAM in axon extension, but not with a precise delineation of pathway boundaries. On myotubes immunoreactivity for NCAM remained low from stage 26 to 30 when it increased dramatically in both aneural and control limbs, indicating that its appearance is not triggered by nerve-dependent activity or trophic interactions. The increase was temporally associated with muscle cleavage and may encourage subsequent axon ramification as well as synaptogenesis. Staining remained high on muscle fibers during secondary myotube formation and only declined during the week before hatching when polyneuronal innervation is withdrawn and the mature synaptic pattern becomes stabilized. This loss of muscle NCAM occurred first on fast and then on slow muscle fibers. Together these results suggest that the timing of innervation may be controlled by the muscle, through NCAM expression, but that the subsequent suppression of muscle NCAM may occur as a result of nerve-mediated activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26222/1/0000302.pd

Adoptionen von Kindern aus Sri Lanka im Kanton St. Gallen 1973-2002

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Polysialylated neuropilin-2 enhances human dendritic cell migration through the basic C-terminal region of CCL21.

Free Access at: http://glycob.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=20488940Dendritic cell (DC) migration to secondary lymphoid organs is a critical step to properly exert its role in immunity; and predominantly depends on the interaction of the chemokine receptor CCR7 with its ligands CCL21 and CCL19. Polysialic acid (PSA) has been recently reported to control CCL21-directed migration of mature DCs. Here; we first demonstrate that PSA present on human mature monocyte-derived dendritic cells did not enhance chemotactic responses to CCL19. We have also explored the molecular mechanisms underlying the selective enhancing effect of PSA on CCL21-driven chemotaxis of DCs. In this regard; we found out that prevention of DC polysialylation decreased CCL21 activation of JNK and Akt signaling pathways; both associated with CCR7-mediated chemotaxis. We also report that the enhanced PSA-mediated effect on DC migration towards CCL21 relied on the highly basic C-terminal region of this chemokine; and depended on the PSA acceptor molecule neuropilin-2 (NRP2) and on the polysialyltransferase ST8SiaIV. Altogether; our data indicate that the CCR7/CCL21/NRP2/ST8SiaIV functional axis constitutes an important guidance clue for DC targeting to lymphoid organs.This work was supported by research grant from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (FISPI0708879 to MAV).Peer reviewe

Identification of embryonic stem cell-derived midbrain dopaminergic neurons for engraftment

Embryonic stem cells (ESCs) represent a promising source of midbrain dopaminergic (DA) neurons for applications in Parkinson disease. However, ESC-based transplantation paradigms carry a risk of introducing inappropriate or tumorigenic cells. Cell purification before transplantation may alleviate these concerns and enable identification of the specific DA neuron stage most suitable for cell therapy. Here, we used 3 transgenic mouse ESC reporter lines to mark DA neurons at 3 stages of differentiation (early, middle, and late) following induction of differentiation using Hes5::GFP, Nurr1::GFP, and Pitx3::YFP transgenes, respectively. Transplantation of FACS-purified cells from each line resulted in DA neuron engraftment, with the mid-stage and late-stage neuron grafts being composed almost exclusively of midbrain DA neurons. Mid-stage neuron cell grafts had the greatest amount of DA neuron survival and robustly induced recovery of motor deficits in hemiparkinsonian mice. Our data suggest that the Nurrl(+) stage (middle stage) of neuronal differentiation is particularly suitable for grafting ESC-derived DA neurons. Moreover, global transcriptome analysis of progeny from each of the ESC reporter lines revealed expression of known midbrain DA neuron genes and also uncovered previously uncharacterized midbrain genes. These data demonstrate remarkable fate specificity of ESC-derived DA neurons and outline a sequential stage-specific ESC reporter line paradigm for in vivo gene discovery