bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variable IgH chain enhancer activity in Burkitt's lymphomas suggests an additional, direct mechanism of c-myc deregulation.
Authors: Jain V K , Judde J G , Max E E , Magrath I T 
Published: December 2022

Abstract
The deregulation of the c-myc gene in small non-cleaved cell lymphomas (SNCL) with 8;14 translocations is thought to be due to the juxtaposition of this gene with the IgH chain locus, but exactly how the Ig locus contributes to the deregulation is unclear. One widely considered hypothesis is that Ig gene enhancers, when moved near c-myc, might stimulate inappropriate transcription of this gene. To evaluate this hypothesis, we have tested the ability of the two known H chain enhancers, the JH-C mu intronic enhancer and the 3' alpha enhancer, to support transcription from c-myc promoters, by using transient transfection assays in a panel of 32 SNCL cell lines with 8;14 translocations. The activity of the JH-C mu intronic enhancer varied widely among the cell lines tested and correlated with the presence of nuclear factors binding to the E4/octamer regions of the enhancer. The 3' alpha enhancer was much less active than the intronic enhancer in all of our cell lines and seems unlikely to account for the c-myc deregulation (although the enhancer we tested was from the rat, because the human homologue is unidentified at present). A marked difference was also seen in the ability of individual cell lines to support transcription from the unenhanced c-myc constructs. Cell lines supporting the lowest enhancer activity tended to support the highest level of transcription from unenhanced c-myc promoters. The differences in transcription from c-myc promoters were confirmed by stably transfecting constructs containing c-myc promoters in SNCL cell lines. Our data strongly suggest that the importance of Ig enhancers for c-myc deregulation varies markedly in different cell lines and that, for many, trans-acting regulators of the c-myc promoters are as important or more important, than Ig enhancers in the deregulation of the c-myc gene.
Partitioning of responder CD8+ T cells in lymph node and lung of mice with Sendai virus pneumonia by LECAM-1 and CD45RB phenotype.
Authors: Hou S , Doherty P C 
Published: December 2022

Abstract
Patterns of LECAM-1 and CD45RB expression have been analysed for mediastinal lymph node (MLN) and bronchoalveolar lavage (BAL) populations from C57BL/6J mice with primary Sendai virus pneumonia. The findings indicate that virus-specific CD8+ CTL precursors differentiate in the regional lymph node and become effector CTL after localization to the virus-infected respiratory tract. Relatively few of the MLN CD8+ T cells were LECAM-1-, and all were CD45RB-hi throughout the acute and recovery phases of this disease process. The CD8+ CD45RB-hi and LECAM-1+ T cells characteristic of the MLN were more apparent in the BAL during the 1st wk after exposure to virus, with this shifting to a predominant CD8+ LECAM-1- CD45RB-lo phenotype from day 10 after infection. In contrast, the CD4+ set was generally CD45RB-lo LECAM-1- in the BAL, although CD4+ CD45RB-lo and LECAM-1- cells maintained at relatively high levels in the MLN. The virus-specific CD8+ effectors found in the BAL from day 8 after infection were uniformly LECAM-1-, but varied in the level of CD45RB expression. Evidence of CTL activity was minimal for the MLN, though virus-specific CTLp were present from day 5 after infection and reached maximum numbers within a further 2 days. The ratio of LECAM-1-:LECAM-1+ CTLp in the MLN ranged from 25:1 to &gt; 200:1, with this pattern being maintained for memory spleen cells recovered 3 mo later. Lack of expression of LECAM-1 is thus characteristic of the great majority of Sendai-virus-specific CD8+ T cells, identified either as effector CTL or as precursors that can be stimulated in vitro under limiting dilution conditions. These lymphocyte populations cannot be discriminated on the basis of hi or lo CD45RB expression.
Overexpression of LFA-1 and ICAM-1 in Down syndrome thymus. Implications for abnormal thymocyte maturation.
Authors: Murphy M , Insoft R M , Pike-Nobile L , Derbin K S , Epstein L B 
Published: December 2022

Abstract
The interaction between lymphocyte function-associated antigen 1 (LFA-1) on thymocytes and intercellular adhesion molecule 1 (ICAM-1) on the thymic stroma plays an important role in thymocyte maturation. Consequently, we examined the constitutive expression of LFA-1 and ICAM-1 in postnatal human thymus from children with Down syndrome (trisomy 21, DS) and age-matched control children. We studied DS thymuses because this aneuploid condition is associated with abnormal thymic anatomy and patterns of thymocyte maturation and the affected individuals have a greatly increased incidence of infection. In addition, the beta-chain for LFA-1 is encoded on human chromosome 21, suggesting that trisomy 21 thymocytes may overexpress this adhesion molecule. Using immunofluorescence and flow cytometry, LFA-1 beta expression was evaluated in eleven pairs of DS and age-matched control thymocytes. The mean channel of fluorescence for LFA-1 beta expression was significantly higher in DS thymocytes than in the controls (p &lt; or = 0.01). Six of the 11 pairs were examined for LFA-1 alpha chain expression. DS thymocytes also showed significantly higher levels of LFA-1 alpha expression (p &lt; or = 0.05), which is consistent with findings that surface expression of the LFA-1 alpha chain is dependent on beta-chain expression. Using immunohistochemical analysis and quantitative video imaging, we examined the level of ICAM-1 expression on frozen sections from four pairs of DS and control thymuses, and found nearly twofold higher levels of ICAM-1 expression in the DS thymuses (p &lt; or = 0.05). DS thymuses also showed a diffuse pattern of ICAM-1 expression with elevated staining in both cortex and medulla and poor demarcation of staining at the cortico-medullary junctions. Given our recent observation that DS thymuses overexpress mRNA for IFN-gamma and TNF, and the fact that both of these cytokines induce ICAM-1 expression on cultured human thymic epithelial cells, we propose that increased levels of IFN-gamma and TNF contribute to the enhanced expression of ICAM-1 in DS thymuses. Our findings support a role for cytokines in the regulation of adhesion molecule expression in the thymus and suggest that the increased expression and abnormal distribution of adhesion molecules in DS thymuses alters the interaction between developing thymocytes and the thymic stroma and results in the abnormal thymocyte maturation observed in DS.
The human Ig-beta cDNA sequence, a homologue of murine B29, is identical in B cell and plasma cell lines producing all the human Ig isotypes.
Authors: Hashimoto S , Gregersen P K , Chiorazzi N 
Published: December 2022

Abstract
The B cell Ag receptor complex consists of at least two disulfide-linked, heterodimeric structures: the clonally restricted membrane Ig (mIg) molecule and the nonpolymorphic Ig-alpha:Ig-beta protein dimer. The latter molecule is encoded by two separate genes, mb-1 and B29. The DNA sequences of murine and human mb-1 and murine B29 have been determined previously. This study describes the sequence of the full-length human cDNA homologue of the murine Ig-beta/B29 message. The human sequence codes for a protein that displays the typical subunit features of a transmembrane member of the Ig superfamily. The transmembrane and intracytoplasmic domains exhibit striking nucleotide and amino acid sequence similarity between the two species. These regions show almost complete conservation of areas presumed to be involved in noncovalent interactions with other members of the receptor complex and with intracellular kinases and cytoskeletal components. The only sequence dissimilarity seen in these presumed critical areas involves the Y-E-G-L-N motif, a potential target for tyrosine phosphorylation. In contrast, the extracellular portion is much more divergent. Inasmuch as similar patterns of species diversity have been reported for Ig-alpha, the Ig-alpha and Ig-beta molecules may have coevolved to maintain species-specific extracellular interactions between one another and with mIg. Similar to the Ig-alpha molecule, the Ig-beta sequence is identical in B lineage cells expressing all five Ig isotypes. However, in contrast to the Ig-alpha molecule, the Ig-beta sequence is expressed at apparently similar levels in terminally differentiated, mIg- plasma cells as well as in mIg+, mature B cells. These data suggest that Ig-beta has functions in addition to those associated with surface mIg expression.
A role for gamma delta + T cells during experimental infection of mice with Leishmania major.
Authors: Rosat J P , MacDonald H R , Louis J A 
Published: December 2022

Abstract
To assess the importance of gamma delta + T lymphocyte responses in experimental murine cutaneous leishmaniasis, the expression of gamma delta + TCR on the surface of lymphocytes in spleen and draining lymph nodes of mice infected with Leishmania major was examined. In both susceptible BALB/c and resistant CBA/J mice, an increase in gamma delta + T cells was observed after s.c. infection. Whereas in chronically infected BALB/c mice, these cells can represent up to 35% of the CD3+ cells in the spleen, in CBA/J mice the percentage of gamma delta + T cells returns to a lower level after resolution of lesions. Further experiments, in which the disease outcome was modified in susceptible BALB/c and in resistant CBA/J mice by chemotherapy or immunointervention, have confirmed that a correlation existed between the multiplication of the parasites and the expansion of gamma delta + T cells in the spleen. Interestingly, in BALB/c mice infected for 4 mo, these gamma delta + T cells represent 80% of the activated blast population and a large proportion of them express the alpha-chain of the CD8 molecule. In an attempt to assess a potential role for the gamma delta + T cells in the control of infection with L. major, the effect of injection of mAb against gamma delta TCR on the course of infection was studied. In both BALB/c and CBA/J mice, blocking of the gamma delta TCR resulted in the development of larger lesions that contained increased numbers of parasites. This treatment significantly delayed the healing of cutaneous lesions in otherwise resistant CBA/J mice. Taken together these results indicate that gamma delta + T cells are expanded during experimental infection of mice with L. major and could be involved in host defense against this parasite.
Reduced contact sensitivity reactions in mice treated with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1.
Authors: Scheynius A , Camp R L , Puré E 
Published: December 2022

Abstract
We have investigated the effect of the administration of mAb against leukocyte function-associated molecule-1 (CD11a/CD18) and intercellular adhesion molecule-1 (CD54) on the delayed-type hypersensitivity reaction in 2,4-dinitro-1-fluorobenzene-sensitized CD2F1 mice. An i.p. injection of the mAb FD441.8 against CD11a at the time of ear challenge led to an almost complete inhibition of ear swelling compared with control animals. Administration of anti-CD54 mAb, 3E2 or YN1/1.7.4, before challenge, resulted in approximately 50% reduction of the delayed-type hypersensitivity response. The decrease in ear swelling reflected a profound inhibition of the edema and the cell infiltration in ears from animals treated with anti-CD11a, and a partial inhibition with anti-CD54 treatment. In addition, the threefold increase in the number of cells recovered from the draining lymph nodes 24 h after challenge in sensitized mice injected with normal IgG was ablated in mice treated with anti-CD11a and partially reduced in anti-CD54-treated animals. Immunohistochemistry and flow cytometry analysis demonstrated that the in vivo administered anti-CD11a mAb was associated with the surface of the majority of the cells in the lymph nodes 24 h after injection and challenge, whereas the anti-intercellular adhesion molecule-1 mAb reacted preferentially with the vascular endothelium. It is concluded that leukocyte function-associated molecule-1 and intercellular adhesion molecule-1 contribute to the generation of an optimal delayed-type hypersensitivity response.
Aberrant expression of the very early activation antigen on MRL/Mp-lpr/lpr lymphocytes.
Authors: Sobel E S , Yokoyama W M , Shevach E M , Eisenberg R A , Cohen P L 
Published: December 2022

Abstract
MRL/Mp-lpr/lpr (MRL/lpr) mice develop marked lymphadenopathy, characterized predominantly by Thy1+CD3+CD4-CD8- cells ("double negative T cells"; DNT). It is paradoxical that DNT proliferate poorly in vitro when stimulated through CD3 or by mitogens. The hamster mAb H1.2F3, raised against dendritic epidermal DNT, recognizes a very early activation (VEA) Ag, which is generally absent on resting cells but expressed soon after T cell activation with ConA or phorbol ester. Cross-linking of this disulfide-linked dimer in the presence of APC and phorbol ester induces proliferation of normal T cells. Therefore, we tested to see whether MRL/lpr DNT expressed this Ag and whether it might play a role in DNT expansion. Unmanipulated cells from enlarged MRL/lpr lymph nodes expressed VEA in an age-dependent manner, peaking at 3 to 4 mo of age. Only limited expression in a small subset of lymphocytes from the congenic MRL/Mp(-)+/+ strain was seen. VEA expression on freshly harvested MRL/lpr lymphocytes was seen mainly on DNT, yet double staining of the DNT for VEA Ag and three other markers known to be present on lpr DNT showed that the DNT were a heterogeneous population. In addition, some CD4+ T cells expressed VEA Ag. Despite their constitutive VEA Ag expression, MRL/lpr DNT showed no proliferative response to cross-linking with the H1.2F3 antibody. Furthermore, unlike normal T cells, they failed to respond to the antibody even when phorbol ester was added. The addition of supplementary cytokines did not correct this defect. These studies indicate that MRL/lpr DNT constitutively and aberrantly express VEA but do not respond when it is cross-linked. These abnormalities may result from the failure to express Fas, the recently reported apoptosis-inducing receptor defective in lpr mice.
Binding of human immunodeficiency virus type-1 to follicular dendritic cells in vitro is complement dependent.
Authors: Joling P , Bakker L J , Van Strijp J A , Meerloo T , de Graaf L , Dekker M E , Goudsmit J , Verhoef J , Schuurman H J 
Published: December 2022

Abstract
The authors studied the binding in vitro of HIV-1 virus particles, conjugated to fluorescein isothiocyanate, to follicular dendritic cells (FDC) isolated from human tonsils. Analysis was done using flow cytometry, fluorescence microscopy, and immunogold electron microscopy. The focus of study was on the effect of serum from various origins, including pooled fresh serum and heated serum from control donors and pooled heated serum from HIV-1-infected patients (containing anti-HIV-1 antibodies). In the presence of heated serum, either from controls or from HIV-1-infected patients, the fluorescence signal in flow cytometry was similar to the background value. In the presence of fresh serum, the signal was substantially increased, and an even higher signal was observed in the presence of fresh serum and serum from HIV-1-infected patients. This high fluorescence signal was also found in the presence of serum depleted of complement factor C5, but not with serum deficient in complement factor C3. The binding of HIV-1 virions to FDC in the presence of fresh serum was confirmed by fluorescence microscopy on cytospot preparations. After quenching of the extracellular fluorescence with trypan blue, the fluorescence was reduced to about 30% of the initial value, indicating that most of bound fluorescent virions were present extracellularly. Similar experiments using blood mononuclear cells showed that fluorescent HIV-1 particles after binding to these cells were present intracellularly. This flow cytometry data was confirmed in immunogold electron microscopy demonstrating that most HIV-1 gag p24 or FITC label was present at the outside of FDC and on adherent virus particles. We conclude that HIV-1 virions adhere to FDC in vitro in a complement component C3-dependent way. Anti-HIV-1 antibodies in serum from HIV-1 infected patients enhance binding but, by itself, are unable to mediate binding.
Proliferation of human T lymphocytes induced with superantigens is not dependent on costimulation by the CD28 counter-receptor B7.
Authors: Damle N K , Klussman K , Leytze G , Linsley P S 
Published: December 2022

Abstract
Staphylococcal enterotoxins, also known as superantigens (SAg), bind class II MHC molecules on APC and upon direct cell-to-cell contact stimulate proliferation of T cells expressing appropriate V beta gene products. The T cell surface molecule CD28 binds its costimulatory counter-receptor, B7 expressed on APC, and augments IL-2 production and T cell growth. Although the role of B7 costimulation during Ag-specific responses of T cells is established, its involvement during the activation of T cells with SAg has not been examined. Using a soluble Ig C gamma 1 chimera of CTLA-4, a second receptor for B7 and a homologue of CD28, this study examines the role of B7 expressed on APC during the induction of proliferation of CD4+ T cells upon stimulation with SAg (SAg/staphylococcal enterotoxins). CTLA-4lg, which has a higher avidity for B7 than CD28, had no effect on the synthesis of IL-2 as well as proliferative responses of CD4+ T cells induced by SAg presented on allogeneic EBV-transformed B cells, and IFN-gamma-activated endothelial cells. In contrast, T cell proliferation induced by alloAg presentation by the same APC was significantly inhibited by CTLA-4lg. mAb directed at the CD11a/CD18 molecule inhibited both SAg-induced and alloAg-induced proliferation of T cells. AlloAg-primed CD4+ T cells, which expressed both class II MHC and intercellular adhesion molecule-1 but not B7, presented SAg to and induced proliferation of both resting and SAg-primed T cells. These responses were inhibited by mAb directed at CD11a/CD18 but not by CTLA-4 Rg. These results suggest that SAg-induced responses differ from those induced by alloAg in that they are not obligatorily dependent on the costimulation by B7. In contrast, adhesive interaction between CD11a/CD18 on T cells and its counter-receptor on SAg-presenting cells is necessary and probably sufficient to support SAg-induced proliferation of T cells.
Isolation and characterization of human peripheral blood dendritic cells.
Authors: Thomas R , Davis L S , Lipsky P E 
Published: December 2022

Abstract
Dendritic cells (DC) are potent APC that can be purified from cultured peripheral blood non-T cells. Because no specific cell surface marker has been found, the lineage of DC remains obscure. The purpose of these studies was to determine the circulating blood cells that could give rise to functional human DC. DC were enriched when purified by standard techniques from non-T cells that were treated with L-leucyl-L-leucine methyl ester, known to be toxic to monocytes and cytolytic cells. To determine whether monocytes or B cells could give rise to DC, fresh non-T cells were sorted into CD14+ monocytes, CD19+ B cells, and CD14- and CD19- cells. Although there was some enrichment for APC function by cultured nonadherent CD14- or CD19- cells, a marked enrichment for cells with dendritic morphology and potent APC function was found in the population that was sorted by the absence of expression of CD14, CD19, CD3, and CD16. More than 90% of the CD14-CD19-CD16-CD3- sorted cells, and of control DC, expressed the myeloid markers CD13 and CD33. Therefore, fresh non-T cells were sorted based on the expression of these myeloid markers. In comparison with CD33-CD14- B cells, some of the CD33+ cells expressed CD14 dimly. However, they were easily distinguished from monocytes, which intensely expressed CD14. CD33+CD14dim cells developed dendritic processes and were more potent APC than control DC, CD33+CD14+, or CD33-CD14- cells. Although freshly isolated CD33+CD14dim DC expressed a number of cell surface molecules also expressed by CD14+ monocytes, they demonstrated lower levels of lysosomal enzymes and a lack of FcR-mediated phagocytosis in comparison with monocytes. Differentiation of morphology and phenotype of CD33+CD14dim cells occurred within 6 to 36 h in culture. However, the CD33+CD14dim cells could effectively function as APC without prolonged preincubation to develop dendritic morphology. These data indicate that human blood DC arise from precursors that express the myeloid lineage markers CD13 and CD33, but are functionally distinct from classic CD14+ monocytes.
Release of nitric oxide during the T cell-independent pathway of macrophage activation. Its role in resistance to Listeria monocytogenes.
Authors: Beckerman K P , Rogers H W , Corbett J A , Schreiber R D , McDaniel M L , Unanue E R 
Published: December 2022

Abstract
Immunodeficient mice are remarkably resistant to Listeria monocytogenes (LM) infection. We examined the role that nitric oxide (NO.) plays in the CB-17/lcr SCID (SCID) response to LM. SCID spleen cells produced large quantities of NO. (as measured by nitrite formation) when incubated in the presence of heat-killed LM. NO. production was dependent on the release of IFN-gamma by the SCID NK cells. When tested directly, macrophages produced large quantities of nitrite in response to LM, but only in the presence of IFN-gamma. The production of NO. induced by LM was not affected by neutralizing antibodies to TNF or IL-1. The production of NO. was inhibited by addition of either of two inhibitors of NO.synthase, NG-monomethyl arginine, or aminoguanidine. In a different situation, NK cells that were stimulated by TNF and Listeria products to release IFN-gamma did not produce NO.. Macrophages cultured with IFN-gamma killed live LM. This increased killing of LM was significantly inhibited by amino-guanidine. In vivo, administration of aminoguanidine resulted in a marked increase in the mortality and spleen bacterial loads of LM-infected SCID or immunocompetent control mice. We conclude that NO. is a critical effector molecule of T cell-independent natural resistance to LM as studied in the SCID mouse, and that the NO.-mediated response is essential for both SCID and immunocompetent host to survive after LM infection.
The fate of Borrelia burgdorferi, the agent for Lyme disease, in mouse macrophages. Destruction, survival, recovery.
Authors: Montgomery R R , Nathanson M H , Malawista S E 
Published: December 2022

Abstract
The macrophage is a known reservoir for a number of infectious agents, and is therefore a likely candidate site for persistence of Borrelia burgdorferi, the Lyme spirochete. We report that unopsonized B. burgdorferi enter macrophages rapidly, resulting mainly in degradation but occasionally in apparent intracellular persistence. We studied uptake of spirochetes by macrophages by simultaneously labeling infected cells with antibodies to B. burgdorferi and with sequential components of the endocytic pathway, and we examined optical sections (0.5-1.0 micron in thickness) of these cells by confocal fluorescence microscopy at multiple time points after infection. We found that only 5 min of incubation at 37 degrees C were required for nearly 100% of B. burgdorferi to enter a lysosomal glycoprotein-positive compartment, whereas 60 min were required for 90% of the spirochetes to appear in a cathepsin L-positive compartment under the same conditions. We also labeled infected living cells with acridine orange to distinguish live from killed intracellular organisms. Although the large majority of spirochetes within a given cell were dead, we saw occasional live ones up to 24 h (the longest interval examined) after all extracellular organisms had been lysed in distilled water. Moreover, we can reculture spirochetes from macrophages after infection. Persistence of spirochetes within macrophages provides a possible pathogenetic mechanism for chronic or recurrent Lyme disease in man.