Different cytokine profiles released by CD4+ and CD8+ tumor‐draining lymph node cells involved in mediating tumor regression

We have previously demonstrated that the growth of weakly immunogenic murine sarcomas leads to the induction of immunologically specific preeffector cells in tumor‐draining lymph nodes (TDLN). The in vitro activation of TDLN cells with anti‐CD3 monoclonal antibodies (mAbs) and interleukin‐2 (IL‐2) resulted in the acquisition of effector function as measured by tumor regression in the adoptive immunotherapy of pulmonary metastases. Further studies were performed to characterize the mechanisms associated with in vivo tumor reactivity mediated by activated TDLN cells. By positive selection, CD4+ and CD8+ T cells were purified and activated by the anti‐CD3/IL‐2 method. CD8+, but not CD4+, cells manifested tumor‐specific granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and interferon‐γ (IFN‐γ) release in vitro, and elicited tumor regression in vivo. By contrast, only activated CD4+ were found to release significant amounts of IL‐2 in response to tumor antigen but did not mediate tumor regression in vivo. Mixing the two purified populations enhanced the antitumor activity of the CD8+ T cells. In culture, IL‐2 was found to augment the relative amount of tumor‐specific release of GM‐CSF and IFN‐γ by activated TDLN cells. We found that the tumor‐specific release of GM‐CSF and IFN‐γ by activated lymphocytes was strongly associated with the in vivo therapeutic efficacy of these cells. Evidence in support of this included the following: (1) cytokine release of TDLN derived after different durations of tumor growth correlated with tumor reactivity in adoptive transfer studies, (2) cytokine release of T cells derived from different lymphoid organs corresponded with tumor reactivity in adoptive transfer, and (3) in vivo administration of neutralizing mAb to IFN‐γ and GM‐CSF significantly inhibited the antitumor reactivity of TDLN cells. These studies document the contributory roles of IFN‐γ, GM‐CSF, and IL‐2 released by activated CD4+ and CD8+ T cells involved in tumor regression. J. Leukoc. Biol. 61: 507–516; 1997.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142128/1/jlb0507.pd

Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway

AbstractZic3 controls neuroectodermal differentiation and left–right patterning in Xenopus laevis embryos. Here we demonstrate that Zic3 can suppress Wnt/β-catenin signaling and control development of the notochord and Spemann's organizer. When we overexpressed Zic3 by injecting its RNA into the dorsal marginal zone of 2-cell-stage embryos, the embryos lost mesodermal dorsal midline structures and showed reduced expression of organizer markers (Siamois and Goosecoid) and a notochord marker (Xnot). Co-injection of Siamois RNA partially rescued the reduction of Xnot expression caused by Zic3 overexpression. Because the expression of Siamois in the organizer region is controlled by Wnt/β-catenin signaling, we subsequently examined the functional interaction between Zic3 and Wnt signaling. Co-injection of Xenopus Zic RNAs and β-catenin RNA with a reporter responsive to the Wnt/β-catenin cascade indicated that Zic1, Zic2, Zic3, Zic4, and Zic5 can all suppress β-catenin-mediated transcriptional activation. In addition, co-injection of Zic3 RNA inhibited the secondary axis formation caused by ventral-side injection of β-catenin RNA in Xenopus embryos. Zic3-mediated Wnt/β-catenin signal suppression required the nuclear localization of Zic3, and involved the reduction of β-catenin nuclear transport and enhancement of β-catenin degradation. Furthermore, Zic3 co-precipitated with Tcf1 (a β-catenin co-factor) and XIC (I-mfa domain containing factor required for dorsoanterior development). The findings in this report produce a novel system for fine-tuning of Wnt/β-catenin signaling

The structure of K- and Cs-monolayers on Cu(0 0 1): diffraction experiments far from the Bragg point

The intensity analysis along the crystal truncation rods has been used to analyse in situ the adsorption behaviour and the structure of K and Cs on Cu(0 0 1) at submonolayer coverages and room temperature. Up to about 0.25 ML K atoms adsorb in hollow sites followed by formation of a quasihexagonal superstructure. In contrast, for Cs adsorption the data can be interpreted by the formation of quasihexagonal Cs islands that grow with increasing coverage. For K an effective radius of 1.6(1) Å independent of coverage is determined. For Cs we fnd d = 2.1 (1) Å after formation of the quasihexagonal superstructure

Frustrated minority spins in GeNi2O4

Recently, two consecutive phase transitions were observed, upon cooling, in an antiferromagnetic spinel GeNi$_2$O$_4$ at $T_{N1}=12.1$ K and $T_{N2}=11.4$ K, respectively \cite{matsuno, crawford}. Using unpolarized and polarized elastic neutron scattering we show that the two transitions are due to the existence of frustrated minority spins in this compound. Upon cooling, at $T_{N1}$ the spins on the \kagome planes order ferromagnetically in the plane and antiferromagnetically between the planes (phase I), leaving the spins on the triangular planes that separate the \kagome planes frustrated and disordered. At the lower $T_{N2}$, the triangular spins also order in the $$ plane (phase II). We also present a scenario involving exchange interactions that qualitatively explains the origin of the two purely magnetic phase transitions

Expression of ZIC family genes in meningiomas and other brain tumors

<p>Abstract</p> <p>Background</p> <p>Zic zinc finger proteins are present in the developing rodent meninges and are required for cell proliferation and differentiation of meningeal progenitors. Although human <it>ZIC </it>genes are known to be molecular markers for medulloblastomas, their expression in meningioma has not been addressed to date.</p> <p>Methods</p> <p>We examined the mRNA and protein expression of human <it>ZIC1</it>, <it>ZIC2</it>, <it>ZIC3</it>, <it>ZIC4 </it>and <it>ZIC5 </it>genes in meningiomas in comparison to other brain tumors, using RT-PCR, analysis of published microarray data, and immunostaining.</p> <p>Results</p> <p><it>ZIC1</it>, <it>ZIC2 </it>and <it>ZIC5 </it>transcript levels in meningiomas were higher than those in whole brain or normal dura mater, whereas all five <it>ZIC </it>genes were abundantly expressed in medulloblastomas. The expression level of <it>ZIC1 </it>in public microarray data was greater in meningiomas classified as World Health Organization Grade II (atypical) than those classified as Grade I (benign). Immunoscreening using anti-ZIC antibodies revealed that 23 out of 23 meningioma cases were ZIC1/2/3/5-immunopositive. By comparison, nuclear staining by the anti-ZIC4 antibody was not observed in any meningioma case, but was strongly detected in all four medulloblastomas. ZIC-positive meningiomas included meningothelial, fibrous, transitional, and psammomatous histological subtypes. In normal meninges, ZIC-like immunoreactivities were detected in vimentin-expressing arachnoid cells both in human and mouse.</p> <p>Conclusions</p> <p>ZIC1, ZIC2, and ZIC5 are novel molecular markers for meningiomas whereas <it>ZIC4 </it>expression is highly selective for medulloblastomas. The pattern of <it>ZIC </it>expression in both of these tumor types may reflect the properties of the tissues from which the tumors are derived.</p

Electronic and Magnetic Properties of Febr2

Electronic and magnetic (e-m) properties of FeBr2 have been surprisingly well described as originating from the Fe2+ ions and their fine electronic structure. The fine electronic structure have been evaluated taking into account the spin-orbit (s-o) coupling, crystal-field and inter-site spin-dependent interactions. The required magnetic doublet ground state with an excited singlet at D=2.8 meV results from the trigonal distortion. This effect of the trigonal distortion and a large magnetic moment of iron, of 4.4 mB, can be theoretically derived provided the s-o coupling is correctly taking into account. The obtained good agreement with experimental data indicates on extremaly strong correlations of the six 3d electrons in the Fe2+ ion yielding their full localization and the insulating state. These calculations show that for the meaningful analysis of e-m properties of FeBr2 the spin-orbit coupling is essentially important and that the orbital moment (0.74 mB) is largely unquenched (by the off-cubic trigonal distortion in the presence of the spin-orbit coupling).Comment: 11 pages in RevTex, 5 figure

Aging, rejuvenation and memory effects in Ising and Heisenberg spin glasses

We have compared aging phenomena in the Fe_{0.5}Mn_{0.5}TiO_3 Ising spin glass and in the CdCr_{1.7}In_{0.3}S_4 Heisenberg-like spin glass by means of low-frequency ac susceptibility measurements. At constant temperature, aging obeys the same `$\omega t$ scaling' in both samples as in other systems. Investigating the effect of temperature variations, we find that the Ising sample exhibits rejuvenation and memory effects which are qualitatively similar to those found in other spin glasses, indicating that the existence of these phenomena does not depend on the dimensionality of the spins. However, systematic temperature cycling experiments on both samples show important quantitative differences. In the Ising sample, the contribution of aging at low temperature to aging at a slightly higher temperature is much larger than expected from thermal slowing down. This is at variance with the behaviour observed until now in other spin glasses, which show the opposite trend of a free-energy barrier growth as the temperature is decreased. We discuss these results in terms of a strongly renormalized microscopic attempt time for thermal activation, and estimate the corresponding values of the barrier exponent $\psi$ introduced in the scaling theories.Comment: 8 pages, including 6 figure

Spin Glasses: Model systems for non-equilibrium dynamics

Spin glasses are frustrated magnetic systems due to a random distribution of ferro- and antiferromagnetic interactions. An experimental three dimensional (3d) spin glass exhibits a second order phase transition to a low temperature spin glass phase regardless of the spin dimensionality. In addition, the low temperature phase of Ising and Heisenberg spin glasses exhibits similar non-equilibrium dynamics and an infinitely slow approach towards a thermodynamic equilibrium state. There are however significant differences in the detailed character of the dynamics as to memory and rejuvenation phenomena and the influence of critical dynamics on the behaviour. In this article, some aspects of the non-equilibrium dynamics of an Ising and a Heisenberg spin glass are briefly reviewed and some comparisons are made to other glassy systems that exhibit magnetic non-equilibrium dynamics.Comment: To appear in J. Phys.: Condens. Matter, Proceedings from HFM2003, Grenobl

Time and length scales in spin glasses

We discuss the slow, nonequilibrium, dynamics of spin glasses in their glassy phase. We briefly review the present theoretical understanding of the spectacular phenomena observed in experiments and describe new numerical results obtained in the first large-scale simulation of the nonequilibrium dynamics of the three dimensional Heisenberg spin glass.Comment: Paper presented at "Highly Frustrated Magnetism 2003", Grenoble, August 200