Role of Common-Gamma Chain Cytokines in NK Cell Development and Function: Perspectives for Immunotherapy

NK cells are components of the innate immunity system and play an important role as a first-line defense mechanism against viral infections and in tumor immune surveillance. Their development and their functional activities are controlled by several factors among which cytokines sharing the usage of the common cytokine-receptor gamma chain play a pivotal role. In particular, IL-2, IL-7, IL-15, and IL-21 are the members of this family predominantly involved in NK cell biology. In this paper, we will address their role in NK cell ontogeny, regulation of functional activities, development of specialized cell subsets, and acquisition of memory-like functions. Finally, the potential application of these cytokines as recombinant molecules to NK cell-based immunotherapy approaches will be discussed

Clostridium botulinum spores and toxin in mascarpone cheese and other milk products

A total of 1,017 mascarpone cheese samples, collected at retail, were analyzed for Clostridium botulinum spores and toxin, aerobic mesophilic spore counts, as well as pH, a(w) (water activity), and Eh (oxidation-reduction potential). In addition 260 samples from other dairy products were also analyzed for spores and botulinum toxin. Experiments were carried out on naturally and artificially contaminated mascarpone to investigate the influence of different temperature conditions on toxin production by C. botulinum. Three hundred and thirty-one samples (32.5%) of mascarpone were positive for botulinal spores, and 7 (0.8%) of the 878 samples produced at the plant involved in an outbreak of foodborne botulism also contained toxin type A. The chemical-physical parameters (pH, a(w), Eh) of all samples were compatible with C. botulinum growth and toxinogenesis. Of the other milk products, 2.7% were positive for C. botulinum spores. Growth and toxin formation occurred in naturally and experimentally contaminated mascarpone samples after 3 and 4 days of incubation at 28 degrees C, respectively

An explanation for the light curve of Jupiter's and Saturn's satellites

Several satellites of Jupiter and Saturn show an asymmetric reflectance between the 'leading' hemisphere (which is generally brighter for the inner satellites of both systems) and the 'trailing' one (which is brighter for the outer satellites Callisto and Iapetus). In order to seek a unified explanation of these observational data it was assumed that, during the final phase of the satellite accumulation process, the surfaces were subjected to a heavy meteoroidal bombardment by the residual bodies in the circumplanetary protosatellite swarms. With suitable hypotheses about the orbital elements of these bodies, the resulting collision rate is anisotropic in an opposite way for inner and outer satellites, with a difference between the two hemispheres of the order of 10-20 percent for all satellites except Iapetus (for which the anisotropy is larger). It is concluded that the model can qualitatively account for the observed effect, even if it is diffcult to propose a detailed mechanism for changing the albedo properties of the satellite surfaces by means of meteoroidal collisions

On the formation and stability of Uranus' rings

The stability of the present configuration of Uranus' rings is discussed, and a possible global model for their formation and evolution is proposed. A ring mass assuring the stability of the epsilon-ring against differential precession is derived and shown to be consistent with that obtained by Goldreich and Tremaine (1979). The long-term stability of the rings against collisional broadening is discussed, and it is shown that the assumption of confinement due only to self-gravitation requires an unacceptably high ring mass, leading to the suggestion that some other confining mechanism is at work. A possible scenario for the origin of the ring system as a result of the tidal break-up of a satellite within the Roche limit is then described

Recombinant IL-21 and anti-CD4 antibodies cooperate in syngeneic neuroblastoma immunotherapy and mediate long-lasting immunity

IL-21 is an immune-enhancing cytokine, which showed promising results in cancer immunotherapy. We previously observed that the administration of anti-CD4 cell-depleting antibody strongly enhanced the anti-tumor effects of an IL-21-engineered neuroblastoma (NB) cell vaccine. Here, we studied the therapeutic effects of a combination of recombinant (r) IL-21 and anti-CD4 monoclonal antibodies (mAb) in a syngeneic model of disseminated NB. Subcutaneous rIL-21 therapy at 0.5 or 1 \u3bcg/dose (at days 2, 6, 9, 13 and 15 after NB induction) had a limited effect on NB development. However, coadministration of rIL-21 at the two dose levels and a cell-depleting anti-CD4 mAb cured 28 and 70 % of mice, respectively. Combined immunotherapy was also effective if started 7 days after NB implant, resulting in a 30 % cure rate. Anti-CD4 antibody treatment efficiently depleted CD4(+) CD25(high) Treg cells, but alone had limited impact on NB. Combination immunotherapy by anti-CD4 mAb and rIL-21 induced a CD8(+) cytotoxic T lymphocyte response, which resulted in tumor eradication and long-lasting immunity. CD4(+) T cells, which re-populated mice after combination immunotherapy, were required for immunity to NB antigens as indicated by CD4(+) T cell depletion and re-challenge experiments. In conclusion, these data support a role for regulatory CD4(+) T cells in a syngeneic NB model and suggest that rIL-21 combined with CD4(+) T cell depletion reprograms CD4(+) T cells from immune regulatory to anti-tumor functions. These observations open new perspectives for the use of IL-21-based immunotherapy in conjunction with transient CD4(+) T cell depletion, in human metastatic NB