The anti-tumor activity of IL-12: Mechanisms of innate immunity that are model and dose dependent

IL-12 has been demonstrated to have potent anti-tumor activities in a variety of mouse tumor models, but the relative roles of NK, NKT, and T cells and their effector mechanisms in these responses have not been fully addressed. Using a spectrum of gene-targeted or Ab-treated mice we have shown that for any particular tumor model the effector mechanisms downstream of IL-12 often mimic the natural immune response to that tumor. For example, metastasis of the MHC class I-deficient lymphoma, EL4-S3, was strictly controlled by NK cells using perforin either naturally or following therapy with high-dose IL-12. Intriguingly, in B16F10 and RM-1 tumor models both NK and NKT cells contribute to natural protection from tumor metastasis, In these models, a lower dose of IL-12 or delayed administration of IL-12 dictated a greater relative role of NKT cells in immune protection from tumor metastasis. Overall, both NK and NKT cells can contribute to natural and IL-12-induced immunity against tumors, and the relative role of each population is turner and therapy dependent.

Coaxial flattening at deep levels of orogenic belts: evidence from blueschists and eclogites on Syros and Sifnos (Cyclades, Greece)

This work presents new Structural data from a high-pressure/low-temperature (HP/LT) metamorphic terrane exposed on the islands of Syros and Sifnos (Cyclades, Greece). The structure and the metamorphism of a relatively coherent HP/LT rock section were studied in order to elucidate how strain was accommodated at deep crustal levels during the formation and exhumation of HP/LT rocks. At least three deformation phases associated with eclogite- and blueschist-facies conditions (P = 8-15 kbar; T = 400-550 degreesC) were recognised. The earliest deformation fabric (S1), preserved as inclusion trails within garnet porphyroblasts, is aligned to define a sub-vertical schistosity (at present orientation), which is frequently orthogonal to the flat matrix schistosity (S2), and may indicate that deep crustal thickening involved upright folding. The currently dominant fabric in the HP rock section, S2, is Usually moderately dipping and locally contains NW-trending glaucophane lineations, symmetric pressure-shadows and eclogitic boudins. The symmetric structures associated with this fabric seem to indicate coaxial vertical thinning, although the existence of non-coaxial structures out of the study area cannot be excluded. Glaucophane-bearing shear bands (S3), with top-to-NW sense of shearing, locally crosscut the earlier structures. The latest recognised fabric (D4) is scarce and often absent within the HP rocks. It is associated with top-to-NE kinematic criteria that formed at greenschist-facies conditions (P = 4-7 kbar; T = 400-450 degreesC). Based on these observations, it is suggested that partitioning of strain occurred at different crustal levels and at different times. Deep crustal deformation was governed by thickening via upright folding followed by coaxial vertical thinning, whereas non-coaxial shearing occurred when the rocks were already exhumed to relatively shallow crustal levels. The earliest fabrics (D1 to D3) pertain to Alpine orogenesis and possibly to syn-orogenic extension, whereas the latest correspond to whole-crust back-are extension. (C) 2002 Elsevier Science Ltd. All rights reserved.