Splenic CD8(+) T cells secrete TGF-beta 1 to exert suppression in mice with anterior chamber-associated immune deviation

Background CD8(+) regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The mechanisms of suppression by CD8(+) T cells in ACAID remain only poorly understood. TGF-beta 1 is considered as an inhibitory cytokine for immunosuppression in some models. The production of TGF-beta 1 by CD8(+) T cells in ACAID, and whether CD8+ T cells exert suppression through TGF-beta 1, is unknown. Methods The suppressive effect of CD8(+) T cells in ACAID mice was determined by a local adoptive transfer (LAT) assay. The production of TGF-beta 1 by CD8(+) T cells was measured by enzyme-linked immunosorbent assay (ELISA). Anti-TGF-beta 1 antibodies were used in the LAT assay to test if they could block the inhibitory effect of CD8(+) T cells. Results CD8(+) T cells from ACAID mice were shown to block the delayed-type hypersensitivity (DTH) response in an antigen-specific manner in a LAT assay. These CD8+ T cells secreted TGF-beta 1, and their suppression could partially be blocked by anti-TGF-beta 1 antibodies. Conclusions Our study confirms that CD8+ T cells from ACAID mice possess inhibitory properties. This population exerts part of its suppressive function via the production of TGF-beta 1

Retinal S-antigen Th1 cell epitope mapping in patients with Behcet's disease

Background - Retinal S-antigen (S-Ag) is a most characterized autoantigen of autoimmune uveitis. The recognized immunodominant epitope of human S-Ag in patients with uveitis has not been identified. In this study, we selected certain patients with active uveitis to map the Th1 cell epitope spectrum of human S-Ag in Behcet's disease(BD). Methods - Blood samples were taken from eight active BD patients who showed an immune response to 40 mixed overlapping peptides spanning the entire sequence of human S-Ag. Peripheral blood mononuclear cells were isolated and stimulated with single S-Ag peptide at 5 mu g/ml or 20 mu g/ml. Single-cell immune responses were measured by IFN-gamma ELIspot assay. Results - BD patients heterogeneously responded to the S-Ag peptides at two concentrations. In general, the responses to 5 mu g/ml peptides were slightly stronger than those to 20 mu g/ml peptides, while the maximum SFC frequency to single peptide at the two concentrations was similar. Several peptides including P31, P35 and P40 induced a prominent response, with the frequency of S-Ag specific cells being about 0.007%. Significant reactivity pattern shift was noted in patients with different disease courses. Conclusions - Certain active BD patients have S-Ag specific Th1 cells with a low frequency. The S-Ag epitope specificity between patients is highly heterogeneous, and varies with the uveitis cours

Final State Rescattering and Color-suppressed \bar B^0-> D^{(*)0} h^0 Decays

The color-suppressed \bar B^0-> D^{(*)0}\pi^0, D^{(*)0}\eta, D^0\omega decay modes have just been observed for the first time. The rates are all larger than expected, hinting at the presence of final state interactions. Considering \bar B^0-> D^{(*)0}\pi^0 mode alone, an elastic D^{(*)}\pi -> D^{(*)}\pi rescattering phase difference \delta \equiv \delta_{1/2} - \delta_{3/2} \sim 30^\circ would suffice, but the \bar B^0-> D^{(*)0}\eta, D^0\omega modes compel one to extend the elastic formalism to SU(3) symmetry. We find that a universal a_2/a_1=0.25 and two strong phase differences 20^\circ \sim \theta < \delta < \delta^\prime \sim 50^\circ can describe both DP and D^*P modes rather well; the large phase of order 50^\circ is needed to account for the strength of {\it both} the D^{(*)0}\pi^0 and D^{(*)0}\eta modes. For DV modes, the nonet symmetry reduces the number of physical phases to just one, giving better predictive power. Two solutions are found. We predict the rates of the \bar B^0-> D^{+}_s K^-, D^{*+}_s K^-, D^0\rho^0, D^+_s K^{*-} and D^0\phi modes, as well as \bar B^0-> D^{0}\bar K^0, D^{*0}\bar K^0, D^{0}\bar K^{*0} modes. The formalism may have implications for rates and CP asymmetries of charmless modes.Comment: REVTeX4, 18 pages, 5 figures, to appear in Phys. Rev.

Charmless Exclusive Baryonic B Decays

We present a systematical study of two-body and three-body charmless baryonic B decays. Branching ratios for two-body modes are in general very small, typically less than $10^{-6}$, except that \B(B^-\to p \bar\Delta^{--})\sim 1\times 10^{-6}. In general, $\bar B\to N\bar\Delta>\bar B\to N\bar N$ due to the large coupling constant for $\Sigma_b\to B\Delta$. For three-body modes we focus on octet baryon final states. The leading three-dominated modes are $\bar B^0\to p\bar n\pi^-(\rho^-), n\bar p\pi^+(\rho^+)$ with a branching ratio of order $3\times 10^{-6}$ for $\bar B^0\to p\bar n\pi^-$ and $8\times 10^{-6}$ for $\bar B^0\to p\bar n\rho^-$. The penguin-dominated decays with strangeness in the meson, e.g., $B^-\to p\bar p K^{-(*)}$ and $\bar B^0\to p\bar n K^{-(*)}, n\bar n \bar K^{0(*)}$, have appreciable rates and the $N\bar N$ mass spectrum peaks at low mass. The penguin-dominated modes containing a strange baryon, e.g., $\bar B^0\to \Sigma^0\bar p\pi^+, \Sigma^-\bar n\pi^+$, have branching ratios of order $(1\sim 4)\times 10^{-6}$. In contrast, the decay rate of $\bar B^0\to\Lambda\bar p\pi^+$ is smaller. We explain why some of charmless three-body final states in which baryon-antibaryon pair production is accompanied by a meson have a larger rate than their two-body counterparts: either the pole diagrams for the former have an anti-triplet bottom baryon intermediate state, which has a large coupling to the $B$ meson and the nucleon, or they are dominated by the factorizable external $W$-emission process.Comment: 46 pages and 3 figures, to appear in Phys. Rev. D. Major changes are: (i) Calculations of two-body baryonic B decays involving a Delta resonance are modified, and (ii) Penguin-dominated modes B-> Sigma+N(bar)+p are discusse

Implications of Recent Measurements of Hadronic Charmless B Decays

Implications of recent CLEO measurements of hadronic charmless B decays are discussed. (i) Employing the Bauer-Stech-Wirbel (BSW) model for form factors as a benchmark, the $B\to\pi^+\pi^-$ data indicate that the form factor $F_0^{B\pi}(0)$ is smaller than that predicted by the BSW model, whereas the data of $B\to\omega\pi, K^*\eta$ imply that the form factors $A_0^{B\omega}(0), A_0^{BK^*}(0)$ are greater than the BSW model's values. (ii) The tree-dominated modes $B\to\pi^+\pi^-, \rho^0\pi^\pm, \omega\pi^\pm$ imply that the effective number of colors N_c(LL) for (V-A)(V-A) operators is preferred to be smaller, while the current limit on $B\to\phi K$ shows that N_c(LR)>3. The data of $B\to K\eta'$ and $K^*\eta$ clearly indicate that $N_c(LR)\gg N_c(LL)$. (iii) In order to understand the observed suppression of $\pi^+\pi^-$ and non-suppression of $K\pi$ modes, both being governed by the form factor $F_0^{B\pi}$, the unitarity angle $\gamma$ is preferred to be greater than $90^\circ$. By contrast, the new measurement of $B^\pm\to\rho^0\pi^\pm$ no longer strongly favors $\cos\gamma<0$. (iv) The observed pattern K^-\pi^+\sim \ov K^0\pi^-\sim {2\over 3}K^-\pi^0 is consistent with the theoretical expectation: The constructive interference between electroweak and QCD penguin diagrams in the $K^-\pi^0$ mode explains why {\cal B}(B^-\to K^-\pi^0)>{1\over 2}{\cal B}(\ov B^0\to K^-\pi^+). (v) The observation \nc(LL)<3<\nc(LR) and our preference for \nc(LL)\sim 2 and \nc(LR)\sim 6 are justified by a recent perturbative QCD calculation of hadronic rare B decays in the heavy quark limit.Comment: 21 pages; CLEO measurements of several charmless B decay modes are updated. Discussion of the unitarity angle gamma in the \rho\pi mode is revise

Charmless Two-body Baryonic B Decays

We study charmless two-body baryonic B decays in a diagramatic approach. Relations on decay amplitudes are obtained. In general there are more than one tree and more than one penguin amplitudes. The number of independent amplitudes can be reduced in the large m_B limit. It leads to more predictive results. Some prominent modes for experimental searches are pointed out.Comment: 15 pages, 2 figures. To appear in Phys. Rev.

Expression and processing of fluorescent fusion proteins of amyloid precursor protein (APP)

AbstractProcessing of β-amyloid precursor protein (APP) by β- and γ-secretases in neurons produces amyloid-β (Aβ), whose excess accumulation leads to Alzheimer's disease (AD). Knowledge on subcellular trafficking pathways of APP and its fragments is important for the understanding of AD pathogenesis. We designed fusion proteins comprising a C-terminal fragment of APP (app) and fluorescent proteins GFP (G) and DsRed (D) to permit the tracking of the fusion proteins and fragments in cells. CAD cells expressing these proteins emitted colocalized green and red fluorescence and produce ectodomains, sGapp and sRapp, and Aβ, whose level was reduced by inhibitors of β- and γ-secretases. The presence of GappR in endosomes was observed via colocalization with Rab5. These observations indicated that the fusion proteins were membrane inserted, transported in vesicles and proteolytically processed by the same mechanism for APP. By attenuating fusion protein synthesis with cycloheximide, individual fluorescent colors from the C-terminus of the fusion proteins appeared in the cytosol which was strongly suppressed by β-secretase inhibitor, suggesting that the ectodomains exit the cell rapidly (t1/2 about 20min) while the C-terminal fragments were retained longer in cells. In live cells, we observed the fluorescence of the ectodomains located between parental fusion proteins and plasma membrane, suggesting that these ectodomain positions are part of their secretion pathway. Our results indicate that the native ectodomain does not play a decisive role for the key features of APP trafficking and processing and the new fusion proteins may lead to novel insights in intracellular activities of APP

Light-Front Approach for Pentaquark Strong Decays

Assuming the two diquark structure for the pentaquark state as advocated in the Jaffe-Wilczek model, we study the strong decays of light and heavy parity-even pentaquark states using the light-front quark model in conjunction with the spectator approximation. The narrowness of the Theta width is ascribed to the p-wave configuration of the diquark pair. Taking the Theta width as a benchmark, we estimate the rates of the strong decays Xi_{3/2}-- to Xi- pi-, Sigma- K-, Sigma_{5c}0 to D_s- p, D_{s0}*- p and Xi_{5c}0 to D_s- Sigma+, D_{s0}^{*-} Sigma+ with Sigma_{5c} Xi_{5c} being antisextet charmed pentaquarks and D_{s0}* a scalar strange charmed meson. The ratio of Gamma(P_c to Baryon D_{s0}*)/Gamma(P_c to Baryon D_s) is very useful for verifying the parity of the antisextet charmed pentaquark P_c. It is expected to be of order unity for an even parity P_c and much less than one for an odd parity pentaquark.Comment: 24 pages, 2 figure

Semi-inclusive B Decays and Direct CP Violation in QCD Factorization

We have systematically investigated the semi-inclusive B decays B->MX, which are manifestations of the quark decay b->Mq, within the framework of QCD-improved factorization. These decays are theoretically clean and have distinctive experimental signatures. We focus on a class of these that do not require any form factor information and therefore may be especially suitable for extracting information on the angles $\alpha$ and $\gamma$ of the unitarity triangle. The nonfactorizable effects, such as vertex-type and penguin-type corrections to the two-body b decay and hard spectator corrections to the 3-body decay are calculable in the heavy quark limit. QCD factorization is applicable when the emitted meson is a light meson or a charmonium. We discuss the issue of the CPT constraint on partial rate asymmetries. The strong phase coming from final-state rescattering due to hard gluon exchange between the final states can induce large rate asymmetries for tree-dominated color-suppressed modes $(\pi^0,\rho^0,\omega)X_{\bar s}$. The nonfactorizable hard spectator interactions in the 3-body decay, though phase-space suppressed, are extremely important for the tree-dominated modes $(\pi^0,\rho^0,\omega)X_{\bar s}, \phi X$, $J X_s,J X$ and the penguin-dominated mode $\omega X_{s\bar s}$. In fact, they are dominated by the hard spectator corrections. Our result for ${\cal B} (B\to J/\psi X_s)$ is in agreement with experiment. The semi-inclusive decay modes: $B^0_s\to (\pi^0,\rho^0,\omega)X_{\bar s}$, $\rho^0X_{s\bar s}$, $B^0\to(K^-X,K^{*-}X)$ and $B^-\to (K^0X_s,K^{*0}X_s)$ are the most promising ones in searching for direct CP violation. In fact, they have branching ratios of order $10^{-6}-10^{-4}$ and CP rate asymmetries of order $(10-40)$.Comment: 28 page

B_c meson rare decays in the light-cone quark model

We investigate the rare decays $B_c \rightarrow D_s(1968) \ell \bar{\ell}$ and $B_c\rightarrow D_s^*(2317) \ell \bar{\ell}$ in the framework of the light-cone quark model (LCQM). The transition form factors are calculated in the space-like region and then analytically continued to the time-like region via exponential parametrization. The branching ratios and longitudinal lepton polarization asymmetries (LPAs) for the two decays are given and compared with each other. The results are helpful to investigating the structure of $B_c$ meson and to testing the unitarity of CKM quark mixing matrix. All these results can be tested in the future experiments at the LHC.Comment: 9 pages, 11 figures, version accepted for publication in EPJ