T cell-specific suppressor factor(s) with regulatory influence on interleukin 2 production and function

In this study we report that alloantigen-activated spleen cells produce both amplifying and suppressive factors under the same conditions. Both types of soluble mediators--as detected in different assay systems-- were present in the supernatants of in vivo sensitized and in vitro restimulated spleen cell populations and were separable by gel filtration. As shown by others, the amplifying factor (IL 2) was eluted in the size range of 30,000 m.w. The suppressive factor(s) (SF) was eluted in the size range of 10,000 m.w. SF was shown to inhibit the proliferative response of T cells to alloantigen, as well as the generation of regulatory T cells and cytotoxic T cells from their precursors when added at the beginning of the in vitro culture. Furthermore, SF inhibited the release of IL 2 from producer T cells but had no detectable effect on the interaction of IL 2 with receptive T cells. In addition it was shown that SF does not affect the generation of PFC from their precursors after activation by T cell-independent antigens. The results indicate that SF selectively acts on T cells and that it is involved in the regulation of the immune response by modulating early events in T cell activation

Deep exclusive charged π\pi electroproduction above the resonance region

A description of exclusive charged pion electroproduction $(e,e'\pi^{\pm})$ off nucleons at high energies is proposed. The model combines a Regge pole approach with residual effect of nucleon resonances. The exchanges of $\pi$(140), vector $\rho(770)$ and axial-vector $a_1(1260)$ and $b_1(1235)$ Regge trajectories are considered. The contribution of nucleon resonances is described using a dual connection between the exclusive hadronic form factors and inclusive deep inelastic structure functions. The model describes the measured longitudinal, transverse and interference cross sections at JLAB and DESY. The scaling behavior of the cross sections is in agreement with JLAB and deeply virtual HERMES data. The results for a polarized beam-spin azimuthal asymmetry in $(\vec{e},e'\pi^{\pm})$ are presented. Model predictions for JLAB at 12 GeV are given.Comment: 29 page

Recognition of viral glycoproteins by influenza A-specific cross- reactive cytolytic T lymphocytes

Two populations of cytolytic T lymphocytes (CTL) generated after influenza A virus infection can be distinguished into one with specificity for the sensitizing hemagglutinin type and a second with cross-reactivity for antigens induced by other type-A influenza viruses. The molecules carrying the antigenic determinants recognized by the cross-reactive CTL were studied. In L-929 cells abortively infected with fowl plague virus, matrix (M) protein synthesis is specifically inhibited, whereas the envelope glycoproteins, hemagglutinin and neuraminidase, are synthesized and incorporated into the plasma membrane. These target cells were lysed by cross-reactive CTL. The envelope proteins of type A/Victoria virus were separated from the other virion components and reconstituted into lipid vesicles that lacked M protein that subsequently were used to prepare artificial target cells. Target-cell formation with vesicles was achieved by addition of fusion-active Sendai virus. These artificial target cells were also susceptible to lysis by cross-reactive CTL. In contrast to previous observations that suggested that the M protein of influenza viruses is recognized by these effector cells, we present evidence that the antigencic determinants induced by the viral glycoproteins are recognized

The cytolytic T lymphocyte response to the murine cytomegalovirus

Limiting dilution (LD) analysis with two modifications, the expansion and the restimulation LD assay, led to the detection and quantification of two distinct in vivo maturation stages within the lineage of virus- specific self-restricted CTL after infection of mice with the murine cytomegalovirus (MCMV). A low frequency set, representing an average of 15% of the specifically activated CTL-P in a draining lymph node, generated virus-specific lytic activity in the absence of antigen, solely under expansion conditions provided by growth and differentiation interleukins. These cells were considered to be active and were denoted antigen-independent or interleukin-receptive CTL-P (IL- CTL-P). A high frequency set required additional antigen in vitro to generate functionally active clones, and therefore the cells were termed antigen-dependent. Both sets are present in vivo simultaneously at the peak of the acute immune response and represent antigen- activated cells because their existence strictly depends on a preceding priming event. IL-CTL-P disappear quickly after acute infection and are absent during the memory state. It is proposed that the isolation of IL- CTL-P could serve to detect viral antigen expression during persistent and/or recurrent herpes virus infections

Systematic Errors in the Estimation of Black Hole Masses by Reverberation Mapping

The mass of the central black hole in many active galactic nuclei has been estimated on the basis of the assumption that the dynamics of the broad emission line gas are dominated by the gravity of the black hole. The most commonly-employed method is to estimate a characteristic size-scale $r_*$ from reverberation mapping experiments and combine it with a characteristic velocity $v_*$ taken from the line profiles; the inferred mass is then estimated by $r_* v_*^2/G$. We critically discuss the evidence supporting the assumption of gravitational dynamics and find that the arguments are still inconclusive. We then explore the range of possible systematic error if the assumption of gravitational dynamics is granted. Inclination relative to a flattened system may cause a systematic underestimate of the central mass by a factor $\sim (h/r)^2$, where $h/r$ is the aspect ratio of the flattening. The coupled effects of a broad radial emissivity distribution, an unknown angular radiation pattern of line emission, and sub-optimal sampling in the reverberation experiment can cause additional systematic errors as large as a factor of 3 or more in either direction.Comment: 19 pages, 4 figures, AASLaTeX, accepted by Ap

Temporal regulation of murine cytomegalovirus transcription and mapping of viral RNA synthesized at immediate early times after infection

The replication of murine cytomegalovirus strain Smith in murine embryonic fibroblasts was investigated at immediate early, early, and late times after infection. Cloned subgenomic HindIII fragments of murine cytomegalovirus DNA served to define the regions of transcription. At immediate early times viral RNA classes ranging in size from 5.1 to 1.05 kilobases (kb) were transcribed mainly from the fragments HindIII-K and -L, whereas low levels of transcription were detected from the two termini HindIII-E and HindIII-N. A characteristic pattern of proteins could be translated from immediate early RNA in vitro. At early and late times after infection transcription from all HindIII fragments occurred, but different patterns of transcripts and proteins could be identified. Inhibitors of DNA synthesis induced differences in the late transcription pattern, located in the HindIII-F fragment. The coding region for abundant immediate early transcription could be located at between 0.769 and 0.817 map units. A plasmic clone containing the main part (0.769 to 0.815 map units) of this region was constructed. This region coded for six polyadenylated immediate early RNA species of 5.1, 2.75, 2.0, 1.75, 1.65, and 1.05 kb in size. Only the 1.75-kb RNA originated entirely from the HindIII-L fragment. The 5.1- and 2.75-kb RNA species were encoded by both the HindIII-L and HindIII-K fragments, and the 2.0-, 1.65-, and 1.05-kb RNA species were entirely transcribed within HindIII-K

Towards next-to-next-to-leading-log accuracy for the width difference in the Bs−BˉsB_s-\bar{B}_s system: fermionic contributions to order (mc/mb)0(m_c/m_b)^0 and (mc/mb)1(m_c/m_b)^1

We calculate a class of three-loop Feynman diagrams which contribute to the next-to-next-to-leading logarithmic approximation for the width difference $\Delta\Gamma_{s}$ in the $B_s-\bar{B}_s$ system. The considered diagrams contain a closed fermion loop in a gluon propagator and constitute the order $\alpha_s^2 N_f$, where $N_f$ is the number of light quarks. Our results entail a considerable correction in that order, if $\Delta\Gamma_{s}$ is expressed in terms of the pole mass of the bottom quark. If the $\overline{MS}$ scheme is used instead, the correction is much smaller. As a result, we find a decrease of the scheme dependence. Our result also indicates that the usually quoted value of the NLO renormalization scale dependence underestimates the perturbative error.Comment: We corrected a typographical mistake in Eq. (4.18), made larger axis labels in Fig.2. Version accepted by JHE

Location, transcripts, and translation products

Cloned genomic fragments from the region (0.769 to 0.818 map units) coding for immediate-early (IE) transcripts of murine cytomegalovirus (MCMV) were used to analyze the physical organization of this region, the direction of transcription, and the proteins synthesized in vitro. Three IE transcription units could be identified. From IE coding region 1 (ie1; 0.781 to 0.796 map units) a dominant 2.75-kilobase (kb) RNA was transcribed from right to left on the prototype arrangement of the MCMV genome which directed the synthesis of an 89,000-molecular-weight polypeptide (89K polypeptide), the major IE protein. This phosphoprotein (pp89) has been shown to be active in the regulation of transcription. Upstream of ie1 and separated by the MCMV enhancer sequence was a second IE coding region, ie2, which was mapped at 0.803 to 0.817 map units. From ie2 a 1.75-kb RNA of moderate abundance was transcribed in the direction opposite to that of the ie1 RNA. After hybrid selection of the ie2 transcript, a 43,000-molecular-weight translation product was detected. A third coding region, ie3, was located directly downstream of ie1 (0.773 to 0.781 map units). The series of RNAs with low abundance, terminating in ie3, probably used the ie1 transcription start site and ranged from 1.0 to 5.1 kb in size. The 5.1-kb RNA apparently represents the nonspliced transcript from both coding regions ie1 and ie3. A 15K polypeptide was translated in vitro from RNA that was hybrid selected by ie3 sequences. Immunoprecipitation with monoclonal antibody revealed that 31K to 67K polypeptides were related to pp89. Some of these proteins were translated from RNAs that were smaller than 2.75 kb. Polypeptides related to pp89 were also synthesized in vivo. Because polypeptides unrelated to pp89 that were translated from RNA that was selected by ie2 and ie3 sequences were not immunoprecipitated by murine antisera, we assumed that the amount of these proteins synthesized in vivo during infection was probably very lo