Langerin expressing cells promote skin immune responses under defined conditions.

There are conflicting data in the literature regarding the role of epidermal Langerhans cells (LC) in promoting skin immune responses. On one hand, LC can be extremely potent APCs in vitro, and are thought to be involved in contact hypersensitivity (CHS). On the other hand, it seems counterintuitive that a cell type continually exposed to pathogens at the organism\'s barrier surfaces should readily trigger potent T cell responses. Indeed, LC depletion in one model led to enhanced contact hypersensitivity, suggesting they play a negative regulatory role. However, apparently similar LC depletion models did not show enhanced CHS, and in one case showed reduced CHS. In this study we found that acute depletion of mouse LC reduced CHS, but the timing of toxin administration was critical: toxin administration 3 days before priming did not impair CHS, whereas toxin administration 1 day before priming did. We also show that LC elimination reduced the T cell response to epicutaneous immunization with OVA protein Ag. However, this reduction was only observed when OVA was applied on the flank skin, and not on the ear. Additionally, peptide immunization was not blocked by depletion, regardless of the site. Finally we show that conditions which eliminate epidermal LC but spare other Langerin(+) DC do not impair the epicutaneous immunization response to OVA. Overall, our results reconcile previous conflicting data in the literature, and suggest that Langerin(+) cells do promote T cell responses to skin Ags, but only under defined conditions.

Infrared spectrum of an extremely cool white-dwarf star

White dwarfs are the remnant cores of stars that initially had masses of less than 8 solar masses. They cool gradually over billions of years, and have been suggested(1,2) to make up much of the 'dark matter' in the halo of the Milky way. But extremely cool white dwarfs have proved difficult to detect, owing to both their faintness and their anticipated similarity in colour to other classes of dwarf stars. Recent improved models(3-5) indicate that white dwarfs are much more blue than previously supposed, suggesting that the earlier searches may have been looking for the wrong kinds of objects. Here we report an infrared spectrum of an extremely cool white dwarf that is consistent with the new models. We determine the star's temperature to be 3,500 +/- 200 K, making it the coolest known white dwarf. The kinematics of this star indicate that it is in the halo of the Milky Way, and the density of such objects implied by the serendipitous discovery of this star is consistent with white dwarfs dominating the dark matter in the halo.

On the parallax of WD 0346+246: a halo white dwarf candidate

We present a parallax measurement for the very cool degenerate WD 0346+246, the serendipitous discovery of which was reported by Hambly et al, We find an absolute parallax of 36 +/- 5 mas, yielding a distance estimate of 28 +/- 4pc. The resulting absolute visual magnitude of the object is M-V = 16.8 +/- 0.3, making it the second-lowest luminosity white dwarf currently known. We use the distance estimate and measured proper motion to show that the object has kinematics consistent with membership of the Galactic halo. WD 0346+246 is therefore by far the coolest and least luminous of only a handful of plausible halo white dwarf candidates. As such, the object has relevance to the ongoing debate concerning the results of microlensing experiments and the nature of any baryonic dark matter component to the Galactic halo residing in stellar remnants.

Use of SLAM and PVRL4 and Identification of Pro-HB-EGF as Cell Entry Receptors for Wild Type Phocine Distemper Virus

Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin β and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin β antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation.