bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two types ofDrosophilaR7 photoreceptor cells are arranged randomly: A model for stochastic cell‐fate determination
Authors: Bell Melanie L. , Earl James B. , Britt Steven G. 
Published: March 2007

AbstractThe R7 photoreceptor cells of theDrosophilaretina are ultraviolet sensitive and are thought to mediate color discrimination and polarized light detection. In addition, there is growing evidence that the color sensitivity of the R8 cell within an individual ommatidium is regulated by a genetic switch that depends on the type of R7 cell adjacent to it. Here we examine the organization of the two major types of R7 cells by three different rigorous statistical methods and present evidence that they are arranged randomly and independently. First, we performed L‐function analyses to test whether the organization of R7 cells (and the relationship between them) is regular, clustered, or completely spatially random. Next, we used generalized linear mixed models to test whether the proportion of R7 cell neighbors differs from their prevalence within the eye as a whole. Finally, we conducted a series of simulations to test whether the proportion of R7 cell neighbors differs from that in a random simulation. In each case, we found evidence that the organization of the two types of R7 cells is random and independent, suggesting that R7 cells in neighboring ommatidia are unlikely to interact and influence each other's identity and may be determined stochastically in a cell‐autonomous manner. Compared with traditional lineage or inductive mechanisms, this may represent a novel mechanism of cell fate determination based on noisy or stochastic gene expression in which the differentiation of an individual R7 cell is a random event but the proportions of R7 cell subtypes are regulated. J. Comp. Neurol. 502:75–85, 2007. © 2007 Wiley‐Liss, Inc.
Homogeneity of intrinsic properties of sexually dimorphic vocal motoneurons in male and female zebra finches
Authors: Roberts Todd F. , Wild J. Martin , Kubke M. Fabiana , Mooney Richard 
Published: March 2007

AbstractSex differences in behavioral repertoires are often reflected in the underlying electrophysiological and morphological properties of motor neurons. Male zebra finches produce long, spectrally complex, learned songs and short calls, whereas female finches only produce short, innate, and spectrally simple calls. In both sexes, vocalizations are produced by using syringeal muscles controlled by motoneurons within the tracheosyringeal part of the hypoglossal motor nucleus (XIIts). We asked whether the sexually dimorphic vocal repertoire of adult zebra finches is paralleled by structural and functional differences in syringeal motoneurons. By using immunohistochemical and intracellular staining methods, we describe sex differences in the morphology of XIIts and its surrounding neuropil (suprahypoglossal region; SH). Although the overall number of XIIts neurons and the proportions of somata/neuropil were not sexually dimorphic, the volumes of both XIIts and SH were larger in males, in part because male XIIts neurons had larger somata. In contrast, female XIIts motoneurons had a more complex dendritic structure than did male neurons, suggesting that the larger volume of the male XIIts is due in part to increased numbers of afferents. Intracellular recordings in brain slices revealed that the intrinsic electrophysiological properties of female XIIts neurons were similar to published values for male XIIts motoneurons. We also show that female neurons received glycinergic inputs from the brainstem respiratory premotor column, similar to those described in males. These findings indicate that male and female zebra finches produce their disparate vocal repertoires using physiologically similar motoneurons. Thus, sites upstream of the motoneuron pool may be the major determinants of sexually dimorphic vocal behaviors in this species. J. Comp. Neurol. 502:157–169, 2007. © 2007 Wiley‐Liss, Inc.
p40, a novel surface molecule involved in the regulation of the non‐major histocompatibility complex‐restricted cytolytic activity in humans
Authors: Poggi Alessandro , Pella Nicoletta , Morelli Luigia , Spada Franca , Revello Valentino , Sivori Simona , Augugliaro Raffaella , Moretta Lorenzo , Moretta Alessandro 
Published: March 2007

AbstractFour monoclonal antibodies (mAb) termed NKTA255, NKTA72, 1F1 and 1B1 were selected on the basis of their ability to inhibit the cytolytic activity of natural killer (NK) cell clones against P815 target cells. These mAb selectively reacted with normal or tumor cells of hematopoietic origin and displayed a cellular distribution similar to that of CD45 or CD11a/CD18 antigens. Immunoprecipitation experiments showed that they reacted with molecules with an apparent molecular mass of 40 kDa under both reducing and nonreducing conditions (“p40” molecules), thus differing from CD45 or CD11a/CD18 antigens as well as from the “inhibitory” receptors for HLA class I molecules (i.e. p58, CD94 and NKB1 molecules). Double‐immunofluorescence analysis of peripheral blood mononuclear cells allowed the identification of three distinct populations on the basis of the fluorescence intensity of cells stained with anti‐p40 mAb. p40bright cells were homogeneously HLA‐DR‐positive, p40medium cells were HLA‐DR‐negative but co‐expressed CD56 antigens, while p40dull cells were all CD3+. Anti‐p40 mAb strongly inhibited the lysis of K562 target cells, mediated by fresh NK cells, as well as the lysis of P815 target cells by NK or T cell clones. In addition, in redirected killing assays, anti‐p40 mAb strongly reduced the anti‐CD16 mAb‐induced cytolytic activity of NK cell clones. On the contrary, they did not inhibit either the anti‐CD3 or anti‐T cell receptor mAb‐mediated cytolytic activity of T cell clones or the lysis of allogeneic phytohemagglutinin blasts mediated by specific cytolytic T cell clones. The p40‐induced inhibition of the NK cytotoxicity required optimal cross‐linking, as anti‐p40 mAb could inhibit the lysis of Fcγ receptor (FcγR)‐positive but not of FcγR‐negative target cells. In addition, (Fab')2 fragments of anti‐p40 mAb failed to inhibit the lysis of FcγR‐positive target cells. In conclusion, p40 molecules represent a new type of inhibitory surface molecule that appears to play a general regulatory role in the NK‐mediated cytolysis.
B7‐1 expression of Langerhans cells is up‐regulated by proinflammatory cytokines, and is down‐regulated by interferon‐γ or by interleukin‐10
Authors: Chang Chung‐Hsing , Furue Masutaka , Tamaki Kunihiko 
Published: March 2007

AbstractLangerhans cells (LC) act as potent antigen‐presenting cells (APC) for primary and secondary T cell‐dependent immune responses. LC express several costimulatory and/or adhesion molecules such as B7/BB1, which has been implicated as one of the important determinants for professional APC. Recent studies have shown that B7/BB1 antigens comprise three distinct molecules termed B7‐1, B7‐2, and B7‐3. We have examined the regulatory properties of B7‐1 expression in LC using various cytokines including interleukin (IL)‐1α, IL‐1β, IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐7, IL‐10, interferon (IFN)‐γ, granulocyte/macrophage colony‐stimulating factor (GM‐CSF), and tumor necrosis factor (TNF)‐α. We have demonstrated: 1) that the B7‐1 expression of LC is reproducibly up‐regulated by either GM‐CSF, TNF‐α, IL‐1α, IL‐1β, or IL‐4 in a dose‐ and time‐dependent manner, 2) that GM‐CSF exhibits the most active effect on B7‐1 up‐regulation in each experiment, 3) that IFN‐γ or IL‐10 profoundly inhibits the B7‐1 expression of LC in a dose‐ and time‐dependent manner, and 4) that the down‐regulatory ability of IFN‐γ or IL‐10 neutralizes the activity of up‐regulatory cytokines. The enhancing or inhibitory action of these cytokines on B7‐1 expression occurs selectively because none of the cytokines consistently affects I‐A expression of LC. These data suggest that the B7‐1 expression of LC may be dynamically regulated by these up‐ and down‐regulatory cytokines in normal and inflammatory epidermal microenvironment.
αEβ7 and α4β7 integrins associated with intraepithelial and mucosal homing, are expressed on macrophages
Authors: Tiisala Sinikka , Paavonen Timo , Renkonen Risto 
Published: March 2007

AbstractThe two β7 integrins αEβ7 and α4β7 are the most recently described members of the integrins participating in intercellular binding. Their expression has been shown to be restricted to leukocytes and they have been suggested to be predominantly found in lymphocytes associating with the epithelium. Expression of β7 has mainly been studied on lymphocytes whereas macrophages have been reported not to express the β7 integrins. In this paper we have studied the expression of β7 integrins in monocytoid cells. The myelomonocytic cell lines HL‐60 and THP‐1 did not express β7 mRNA or protein, but differentiation of these cell lines to macrophages with phorbol 12‐myristate 13‐acetate (PMA) led to a strong induction of the β7 mRNA expression. A clear but less pronounced up‐regulation of β7 mRNA‐expression was also seen after treatment of HL‐60 and THP‐1 cells with interferon‐γ (IFN‐γ). However, its up‐regulating effect on the surface expression of α4β7 and αE7 complexes (detected by the monoclonal antibodies Act I and HML‐1, respectively) exceeded that observed with PMA. To verify the in vitro cell line observations with normal cells, we also studied peripheral blood monocytes and tissue macrophages. Peripheral blood monocytes were Act I− and HML‐1− in flow cytometry, but their expression was increased after a 72‐h culture in the presence of PMA or IFN‐γ. Also, several Act I+ and HML‐1+ macrophages were found in immunohistochemical stainings of both liver and edemic lung biopsies as well as in lymph node sinuses. We therefore conclude that while monocytes do not express β7 integrins the more differentiated cells of the monocyte‐macrophage lineage do express both the α4β7 and αEβ7 integrins, which might play a role in their intraepithelial homing.
Hypomethylation of the interferon‐γ gene correlates with its expression by primary T‐lineage cells
Authors: Melvin Ann J. , McGurn Mary E. , Bort Susan J. , Gibson Christine , Lewis David B. 
Published: March 2007

AbstractTo determine the potential role of methylation in the regulation of interferon‐γ (IFN‐γ) gene transcription by T cells, primary T‐lineage cell populations were analyzed for the extent of methylation of three CpG sites within or near transcriptional activator elements in the 5′ flank and first intron of the human IFN‐γ gene. A striking correlation was observed between the capacity of the IFN‐γ gene to be expressed and the degree of hypomethylation. The IFN‐γ gene was virtually completely methylated at all sites in thymocytes, neonatal T cells, and adult CD45RAhiCD45R0lo (antigenically naive) CD4 T cells, cell types that all have a low or undetectable capacity to express the IFN‐γ gene. In contrast, there was substantial hypomethylation in T‐lineage cell types with relatively high capacities to express the IFN‐γ gene, including adult CD8 T cells and adult CD45RAloCD45R0hi (memory/effector) CD4 T cells. These results suggest that hypomethylation of the IFN‐γ genetic locus may be an important determinant of IFN‐γ gene expression in vivo by T‐lineage cells.
Thymic epithelium induces full tolerance to skin and heart but not to B lymphocyte grafts
Authors: Thomas‐Vaslin Véronique , Salaün Josselyne , Gajdos Benoǐt , le Douarin Nicole , Coutinho Antonio , Bandeira Antonio 
Published: March 2007

AbstractAthymic nude mice reconstituted at birth with allogeneic thymic epithelia (TE) from day 10 embryos (E10), show life‐long specific tolerance to skin and heart grafts, but eliminate B lymphocytes of the TE donor haplotype, nearly as well as those from a third strain. Previous immunizations with B cells do not alter the state of tolerance to skin grafts, but specifically accelerate elimination of lymphocytes. In contrast, transplantation of E15 allogeneic thymuses already seeded by hematopoietic cells resulted in chimeras tolerant to both skin and B lymphocytes. In vitro reactivities towards stimulator spleen cells of the haplotype of the thymus were observed in both E10 TE and E15 thymus chimeras.We conclude that induction of full in vivo tolerance to B cells requires hematopoietic cells, while this is not the case for induction of tolerance to skin and heart tissues; furthermore, in vitro reactivity to stimulator spleen cells of the tolerized haplotype is independent of in vivo tolerance.
Role of CD44 cytoplasmic domain in hyaluronan binding
Authors: Perschl Astrid , Lesley Jayne , English Nicole , Trowbridge Ian , Hyman Robert 
Published: March 2007

AbstractThe hyaluronan (HA) binding activity of mutant CD44 constructs expressed in AKR1 T‐lymphoma cells was evaluated by flow cytometry using fluoresceinconjugated HA (Fl‐HA). Previous studies showed that wild‐type hematopoietic CD44 bound Fl‐HA when expressed in AKR1, but that truncated “tailless” CD44, lacking all but six amino acids of the cytoplasmic domain, did not bind. Here, we show that a disulfide‐bonded dimer of CD44, formed by substituting the transmembrane region of CD3ζ chain for that of CD44, binds Fl‐HA, even when the cytoplasmic domain of the CD44 dimer is absent. We conclude that dimerization of CD44 abrogates the requirement for the cytoplasmic domain, suggesting that the cytoplasmic domain of CD44 may contribute to HA binding by promoting CD44 clustering. These results suggest that changes in the distribution of CD44 on the cell surface, induced by molecular interactions either from within the cell or from outside, may regulate its role as a receptor. Further studies sought to localize the region of the CD44 cytoplasmic domain contributing to HA binding by the construction of a series of cytoplasmic domain truncation mutants and internal deletion mutants. All of the mutant CD44 molecules bound Fl‐HA similarly to wild‐type CD44. Thus, it was not possible to assign the function mediating HA binding to a specific region of the cytoplasmic domain, suggesting either that multiple regions of the cytoplasmic domain can promote enhancement of HA binding, or that the role of the cytoplasmic domain in mediating this function does not require a specific amino acid sequence.
Expression of TAP1 by human trophoblast
Authors: Clover Linda M. , Sargent Ian L. , Townsend Alain , Tampé Robert , Redman Chris W. G. 
Published: March 2007

AbstractSuccessful placentation in the human is dependent on the trophoblast evading recognition and destruction by the maternal immune system. However, invasive cytotrophoblast express HLA‐G which may be able to present peptide to T cells. Transporter proteins are essential for peptide presentation and major histocompatibility complex (MHC) class I assembly. We have determined their expression by trophoblast in relation to HLA‐G, using immunohistochemistry. Antitransporter protein antibody (TAP1) labeling closely paralleled that of MHC class I, but the intensity of its expression was much greater on the HLA‐G+ extravillous cytotrophoblast than any other fetal or maternal tissue in the first trimester and at term. This suggests that the extravillous cytotrophoblast are very actively assembling MHC class I antigens with peptides. However, expression of MHC class I by the cytotrophoblast was not correspondingly elevated. This pattern could result from HLA‐G being shed from the surface of the trophoblast, a process which may play a central role in protecting the fetus from maternal immune attack.
Ovalbumin injected with complete Freund's adjuvant stimulates cytolytic responses
Authors: Ke Yong , Li Ying , Kapp Judith A. 
Published: March 2007

AbstractCD8+ cytotoxic T lymphocytes (CTL) recognize antigens (Ag) associated with class I major histocompatibility complex (MHC) molecules. Endogenously synthesized protein Ag are processed into peptides in the cytoplasm and transported to the endoplasmic reticulum where they are bound by class I proteins. Exogenous Ag do not enter the class I processing pathway of most cells and thus do not activate CD8+ CTL. Nevertheless, several investigators have reported that immunization with exogenous Ag can activate CD8+ T cells that have immunoregulatory activity. To determine how exogenous Ag entered the class I pathway in vivo and whether immunosuppressive CD8+ T cells were cytolytic, we have shown in this report that injection with OVA emulsified in the complete Freund's adjuvant (CFA) primed CD8+, class I MHC‐restricted, OVA‐specific CTL in mice. These CTL recognize the OVA257–264 epitope, produce tumor necrosis factor‐α and interferon‐γ upon activation. Both oil and mycobacteria components in CFA were required for inducing CTL responses. Priming was not attributed to direct sensitization of class I‐bearing cells by contaminating peptides. Rather, phagocytic cells, but not CD4+ helper T cells, were required for priming CD8+ CTL by OVA‐CFA. Thus, OVA in CFA is taken up by antigen‐presenting cells and processed into the class I pathway by phagocytic cells in vivo. In addition, CTL induced by OVA‐CFA suppressed the antibody response to OVA in adoptive recipients. These results suggest that CD8+ CTL specific for exogenous proteins might be routinely stimulated by injecting proteins in conventional adjuvants and that such cells have the potential to regulate immune responses in vivo.
Mimicking the humoral immune response in vitro results in antigen‐specific isotype switching supported by specific autologous T helper cells: generation of human HIV‐1‐neutralizing IgG monoclonal antibodies from naive donors
Authors: Chin Lie‐Te , Malmborg Ann‐Christin , Kristensson Karin , Hinkula Jorma , Wahren Britta , Borrebaeck Carl A. K. 
Published: March 2007

AbstractMolecular and cellular requirements for antigen‐specific isotype switch of human B cells have been investigated by mimicking signaling occurring in germinal centers. Peripheral blood mononuclear cells from healthy seronegative blood donors were first primary immunized in vitro, using a synthetic immunogen containing both a T and B cell epitope, which generated specific IgM‐secreting B cells. We used the apex of the V3 loop of gp120 as B cell epitope linked to a promiscuous T helper epitope from tetanus toxin. In parallel, CD4+ T helper cell clones specific for the T epitope of the immunogen were established. In a secondary in vitro stimulation period, we co‐cultured the antigen‐specific T and B cells on CD32‐transfected fibroblasts, together with an anti‐CD40 monoclonal antibody. This resulted in isotype switching and human antigen‐specific, IgG‐secreting B cells were detected. This response was strictly dependent upon the presence of autologous T helper cells and the immunogen. Antigen‐specific human B cells derived from this primary and secondary in vitro immunization were subsequently subjected to electrofield‐induced somatic cell hybridization and hybridomas secreting human anti‐V3 IgG monoclonal antibodies were isolated. One human antibody was further characterized and shown to be specific for the immunizing antigen with an affinity constant of 24 nM. This antibody also effectively neutralized different isolates of HIV‐1, achieving a 50% neutralization at 0.46 μg/ml.
Regulation of the interaction between Th1 and Th2 T cell clones to provide help for antibody production in vivo
Authors: Rizzo Luiz V. , Dekruyff Rosemarie H. , Umetsu Dale T. , Caspi Rachel R. 
Published: March 2007

AbstractOn the premise that an individual with an intact immune system has the capability to develop both cellular and antibody immune responses supported by the balance between the lymphokines secreted by T helper (Th) cells, we studied the interaction between different types of Th cell clones in vivo and the parameters that may affect this interaction. We used an adoptive transfer system in which nude or lethally irradiated mice were reconstituted with histocompatible CD4+ keyhole limpet hemocyanin (KLH)‐specific T cell clones with defined lymphokine profiles. This approach allowed us to study the effects of the cognate interaction between T and B cells in the presence of a defined set of lymphokines. We demonstrated that the co‐transfer of both subsets of Th cells resulted in increased production of IgA, and decreased production of IgE and IgG2a. The concomitant presence of both cell types also increases their functional survival in vivo. We have shown that in the presence of a Th2 clone, higher immunization doses (above 100 μg trinitrophenol (TNP)‐KLH/mouse) result in increased production of IgE and IgG1. In contrast, when a Th1 clone is present, low immunization doses (less than 50 μg TNP‐KLH/mouse) resulted in increased production of IgG2a. We were also able to show that the neutralization of interleukin‐4 (IL‐4) and or interferon‐γ (IFN‐γ) was sufficient to abrogate most of the regulatory effects caused by the Th2 or the Th1 clone respectively. Our results indicate that the subset of T cell(s) transferred determines the type of response obtained. In addition, the data presented indicate that the antigen dose used for immunization can modulate the quantitative parameters of the response. Furthermore, we have shown that the interaction between the two subsets of T cells in vivo is characterized by both antagonistic and agonistic effects and that most of the regulatory effects exerted by one subset over the other are mediated by IL‐4 or IFN‐γ.
Molecular characterization of leukocyte adhesion deficiency in six patients
Authors: Wright Ann H. , Douglass Wendy A. , Taylor G. Malcolm , Lau Yu‐Lung , Higgins David , Davies Kevin A. , Law S. K. Alex 
Published: March 2007

AbstractLeukocyte adhesion deficiency (LAD) is caused by defects in the CD18 gene, which codes for the common β2 subunit of the leukocyte integrins LFA‐1, Mac‐1 and p150,95. Failure to produce a functional β2 subunit results in the defective expression of all three leukocyte integrins, and the leukocytes of LAD patients have subnormal adhesion properties. Six patients with LAD were studied. Patient B was homozygous and carried a G284S mutation. A two‐bp (GA) deletion at position 1256 (1256ΔGA) was found in the cDNA of patient C, who also had an abnormally large mRNA of 4.3 kb. Patients E and K were siblings and were heterozygous at the genomic level. One defective allele contained a mutation in intron 6/7 which created a preemptive 3′ splice site. The resulting mRNA has 12 extra bases at the junction of exons 6 and 7, coding for four extra residues PSSQ in the protein. The same allele also carried a R586W mutation. The other allele was transcribed at a low level and was not characterized. Patient G carried a L149P mutation in one allele; again, the other allele was not characterized due to low transcription levels. Patient R carried two mutant alleles with G284S and R593C mutations respectively. The G284S mutation and the 1256ΔGA deletion have not been reported previously. CD18 cDNA carrying the abnormalities were cotransfected with normal CD11a or CD11b cDNA into COS cells. Expression of the LFA‐1 (CD11a/CD18) and Mac‐1 (CD11b/CD18) antigens on COS cells was not detected, suggesting that these two mutations are sufficient to account for LAD.