bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-specific pulmonary secretory antibody response.
Authors: Abraham E , Shah S 
Published: December 2022

Abstract
Secretory IgA (sIgA) present at mucosal surfaces such as the lungs and intestine plays an important role in resistance to infection occurring at these anatomic sites. Because IL-2 and IL-4 can augment B cell proliferation and Ig production, we investigated possible adjuvant effects of these cytokines on bacterial polysaccharide-specific pulmonary sIgA generation. As shown in previous studies, intranasal immunization with liposomes containing bacterial polysaccharide from Aerobacter levanicum and Pseudomonas aeruginosa resulted in increased numbers of bacterial polysaccharide-specific pulmonary plasma cells and sIgA titers, compared with those found in unimmunized mice. Inclusion of IL-2, but not IL-4, into the intranasally administered liposomes further increased titers of bacterial polysaccharide specific sIgA and pulmonary plasma cells. Intranasal vaccination with liposomes containing bacterial polysaccharide and 10 micrograms/kg IL-2 increased bacterial polysaccharide-specific pulmonary plasma cell numbers by more than 80-fold compared with the response in mice immunized with liposomes containing bacterial polysaccharide, but without IL-2. The percentage of pulmonary plasma cells producing antibody to polysaccharide from A. levanicum rose from 0.14% in mice intranasally immunized with liposomes containing only polysaccharide to 4.1% in animals vaccinated with liposomes containing polysaccharide and IL-2. Intranasal immunization with liposomes containing P. aeruginosa polysaccharide and IL-2 significantly reduced mortality from P. aeruginosa pneumonia. These results demonstrate that IL-2 has potent adjuvant effects on bacterial Ag-specific sIgA production in the lungs when included in intranasally administered liposomes.
Role of antigen-specific T cell help in the generation of in vivo antibody responses. I. Antigen-specific T cell help is required to generate a polyclonal IgG1 response in anti-IgD antibody-injected mice.
Authors: Morris S C , Lees A , Inman J , Finkelman F D 
Published: December 2022

Abstract
A system in which injection of mice with an antibody to mouse IgD that they recognize as foreign stimulates a large, T cell-dependent IgG response was used to study whether Ag-specific T cell help is required to stimulate polyclonal (non-Ag-specific) IgG production in vivo. Igha x Ighb allotype heterozygous mice were injected with a conjugate of a foreign Ag coupled to a mAb specific for one of the two IgD allotypes expressed in these mice. This conjugate cross-links mIgD on B cells that express the recognized allotype. These cells process the conjugate and present the foreign Ag to Ag-specific T lymphocytes, which become activated. Thus, B cells of the recognized allotype can be stimulated by cross-linking of their mIgD, Ag-specific T cell help, non-Ag-specific cytokines, and non-Ag-specific contact with activated T cells. In contrast, B cells that express the Igh allotype not recognized by the Ag-anti-IgD antibody conjugate (bystander B cells) can be stimulated in this system only by non-Ag-specific cytokines and non-Ag-specific contact with activated T cells. Although both recognized and bystander B cells in conjugate-injected mice demonstrated substantial increases in size and Ia expression, only the recognized B cells were induced to synthesize DNA and to make a substantial polyclonal Ig response. Bystander B cells still failed to secrete IgG when mice were injected with an anti-IgD-Ag conjugate specific for the other Igh allotype as well as a mAb that cross-linked IgD of the bystander B cell allotype. These observations demonstrate that although non-Ag-specific cytokine and contact-mediated T cell help are sufficient to induce B cells to increase in size and Ia expression in anti-IgD antibody-injected mice, Ag-specific T cell help is required to stimulate the generation of an IgG response in these mice.
Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes. An essential role for keratinocyte-derived IL-10.
Authors: Rivas J M , Ullrich S E 
Published: December 2022

Abstract
Exposing murine keratinocyte cultures to UV radiation causes the release of a suppressive cytokine that mimics the immunosuppressive effects of total-body UV exposure. Injecting supernatants from UV-irradiated keratinocyte cultures into mice inhibits their ability to generate a delayed-type hypersensitivity reaction against allogeneic histocompatibility Ag, and spleen cells from mice injected with supernatant do not respond to alloantigen in the in vitro MLR. A unique feature of the immunosuppression induced by either total-body UV-exposure or injecting the suppressive cytokine from UV-irradiated keratinocytes is the selectivity of suppression. Although cellular immune reactions such as delayed-type hypersensitivity are suppressed antibody production is unaffected. Because the selective nature to the UV-induced immunosuppression is similar to the biologic activity of IL-10, we examined the hypothesis that UV exposure of keratinocytes causes the release of IL-10. Keratinocyte monolayers were exposed to UV radiation and at specific times after exposure mRNA was isolated or the culture supernatant from the cells was collected. IL-10 mRNA expression was enhanced in UV-irradiated keratinocytes. The secretion of IL-10 by the irradiated keratinocytes was determined by Western blot analysis. A band reactive with anti-IL-10 mAb was found in supernatants from the UV-irradiated but not the mock-irradiated cells. IL-10 biologic activity was determined by the ability of the supernatants from the UV-irradiated keratinocytes to suppress IFN-gamma production by Ag-activated Th 1 cell clones. Anti-IL-10 mAb neutralized the ability of supernatants from UV-irradiated keratinocytes to suppress the induction of delayed-type hypersensitivity in vivo. Furthermore, injecting UV-irradiated mice with antibodies against IL-10 partially inhibited in vivo immunosuppression. These data indicate that activated keratinocytes are capable of secreting IL-10 and suggest that the release of IL-10 by UV-irradiated keratinocytes plays an essential role in the induction of systemic immunosuppression after total-body UV exposure.
Increased avidity of mutant IgM antibodies caused by the absence of COOH-terminal glycosylation of the mu H chain.
Authors: Bazin R , Darveau A , Martel F , Pelletier A , Piché L , St-Laurent M , Thibault L , Demers A , Boyer L , Lemieux G 
Published: December 2022

Abstract
We have previously described the isolation of two hybridoma variants secreting higher avidity IgM (D5 and 7F5), starting from the E11 hybridoma cell line, which produces an antibody specific for the A Ag of the ABO blood group system. In order to explain at the molecular level this increased reactivity, cDNA encoding the H and L chains of the E11, D5, and 7F5 mAb were cloned and sequenced. Comparison of the nucleotide sequences showed a single point mutation in each of the two mAb produced by the hybridoma variants. The mutations were both located in the H chain C region and caused a Ser to Phe substitution at position 565 in the D5 mAb and a Asn to Tyr substitution at position 563 in the 7F5 mAb. Both substitutions modified the consensus glycosylation sequence (Asn-X-Ser/Thr) located in the tail piece of the secretory mu-chain. The absence of glycosylation at this site was confirmed by CNBr cleavage of the [14C]mannose-labeled mAb. The two single point mutations were solely responsible for the increased avidity of the antibodies, as confirmed by site-directed mutagenesis of the E11 mu-chain and serologic analysis of the mutated E11 antibodies. We conclude that the absence of glycosylation at Asn 563 is responsible for the increased avidity of the mutant, possibly by altering the quaternary structure of the IgM polymer. To our knowledge, this is the first report that point mutations in the H chain C region can influence the reactivity of IgM mAb.
L chain isotype regulation in horse. I. Characterization of Ig lambda genes.
Authors: Home W A , Ford J E , Gibson D M 
Published: December 2022

Abstract
Analysis of 10 cDNA encoding lambda L chains of horse Ig indicated that this species may employ a relatively small number of variable region (V lambda) genes in the splenic B cell population. The V lambda sequences of all of the cDNA analyzed were closely related (&gt; 88% identity at the nucleotide level) and were characterized by a deletion of the amino acid residue at position 3 compared with V lambda sequences so far described in other species. The 10 V lambda sequences could be grouped into three groups, V lambda 1 to V lambda 3, on the basis of a number of linked substitutions. Sequences within the groups showed the greatest divergence in the third cdr regions and at the V-J junctions. The junctional variation included amino acid substitutions on both sides of the V-J junction as well as the insertion or deletion of two to four amino acid residues. Four C lambda genes were identified in genomic blots of horse DNA, and three of these were found expressed in splenic cDNA. The fourth C lambda gene may represent a pseudogene, inasmuch as the associated J region possessed a defective heptamer joining sequence. Six of the nine possible V lambda-C lambda combinations were found in the cDNA analyzed, suggesting that genes belonging to groups V lambda 1 through V lambda 3 may rearrange to any one of three J lambda-C lambda genes. One V lambda germline gene was characterized and found to represent a distinct V lambda group (V lambda 4), not represented in the cDNA sequences analyzed. The number of germline V lambda genes was estimated to be 20 to 30, based on analysis of restriction fragments hybridizing with V lambda probes. On the basis of these data, we propose that the V lambda repertoire in horse may consist of relatively limited number of genes, of which only a few may be used at high frequency in the splenic B cell population. The results indicate that predominance of lambda-chains in horse Ig may not simply be due to the presence of a large germline V lambda gene repertoire.
V delta 1+ subset of human gamma delta T cells responds to ligands expressed by EBV-infected Burkitt lymphoma cells and transformed B lymphocytes.
Authors: Häcker G , Kromer S , Falk M , Heeg K , Wagner H , Pfeffer K 
Published: December 2022

Abstract
Human gamma delta T cells of peripheral blood can be divided in two groups in terms of their TCR as well as their behavior upon in vitro stimulation. The major subset expresses the TCR V-segments V gamma 9 and V delta 2 and proliferates in response to ligands revealed by various microorganisms, and the cell line Daudi in addition. The minor group is less homogenous on the gamma-chain but is almost completely identified by mAb against the V delta 1 segment; there is no ligand known to promote growth of these cells. Here we demonstrate that gamma delta T cells out of this subgroup are strongly stimulated in vitro by cells from several Burkitt's lymphoma cell lines. EBV infection of the Burkitt's lymphoma cell lines enhanced the stimulatory ability towards the T cells. Although EBV infection influenced the expression of a variety of cell surface molecules including ICAM-1 and LFA-3, no correlation to the gamma delta T cell-stimulating capacity became apparent. We conclude that Burkitt's lymphoma cells and transformed B cells express ligands of cellular origin for a hitherto poorly characterized subgroup of human gamma delta T cells.
Highly diverse T cell recognition of a single Plasmodium berghei peptide presented by a series of mutant H-2Kd molecules.
Authors: Jaulin C , Casanova J L , Romero P , Luescher I , Cordey A S , Maryanski J L , Kourilsky P 
Published: December 2022

Abstract
We have tested 21 independent CTL clones for recognition of a single peptide derived from the Plasmodium berghei circumsporozoite protein in the context of 13 mutants of the murine MHC class I molecule H-2Kd. In this series of Kd mutants, amino acid residues located on the upper surface of the alpha-helices were individually substituted by alanine. Remarkably, most clones displayed individual recognition patterns on the Kd mutants. We had previously found that this series of CTL clones was likewise highly diverse in terms of both TCR primary structure and peptide fine specificity. Our data thus reinforce the concept that multiple T cell epitopes are available on the surface of a single peptide-MHC class I complex for recognition by specific TCR.
Transfection of mouse cytotoxic T lymphocyte with an antisense granzyme A vector reduces lytic activity.
Authors: Talento A , Nguyen M , Law S , Wu J K , Poe M , Blake J T , Patel M , Wu T J , Manyak C L , Silberklang M 
Published: December 2022

Abstract
Murine CTL have seven serine proteases, known as granzymes, in their lytic granules. Despite considerable effort, convincing evidence that these enzymes play an obligatory role in the lytic process has not been presented. To investigate the function of one of these proteases, granzyme A (GA), we utilized an antisense expression vector to lower the level of the enzyme in the cells. An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1. Transfectants were selected based on resistance to hygromycin B, and a number of stable lines were developed. One of the antisense lines had greatly reduced levels of GA mRNA, when compared to the parental cells or to control lines transfected with the vector lacking the antisense DNA. The message levels for two other CTL granule proteins, granzyme B and perforin, were unaffected by the antisense vector. The amount of GA, as measured by enzymatic activity, was 3- to 10-fold lower in the transfectant. Most significantly, this line also consistently showed 50 to 70% lower ability to lyse nucleated target cells and to degrade their DNA. Furthermore, it exhibited 90 to 95% lower lytic activity to anti-CD3-coated SRBC. Conjugate formation with target cells, however, was normal. These data provide strong evidence that GA plays an important role in the cytolytic cycle, and that the quantity of enzyme is a limiting factor in these cytolytic cells.
Infection of human natural killer (NK) cells with replication-defective human T cell leukemia virus type I provirus. Increased proliferative capacity and prolonged survival of functionally competent NK cells.
Authors: Lo K M , Vivier E , Rochet N , Dehni G , Levine H , Haseltine W A , Anderson P 
Published: December 2022

Abstract
Human T-cell leukemia virus type I (HTLV-I) can infect a variety of human cell types, but only T lymphocytes are efficiently immortalized after HTLV-I infection. This study reports an attempt to infect and to immortalize NK cells with HTLV-I. Co-cultivation of freshly isolated NK cells with a HTLV-I-producing T cell line did not result in NK cell infection. However, NK cells activated with an anti-CD16 mAb and co-cultivated with a HTLV-I-producing T cell line were reproducibly infected by HTLV-I. HTLV-I infection was documented in NK cell lines and clones by the detection of defective integrated provirus by both Southern blot and polymerase chain reaction analysis. Although HTLV-I-infected NK cells produced viral proteins, they did not produce infectious viral particles. HTLV-I-infected NK cells were phenotypically indistinguishable from their uninfected counterparts (CD16+, CD2+, CD56+, CD3-). They also retained the ability to mediate both natural and antibody-dependent cell cytotoxicity. The IL-2-dependent proliferation of HTLV-I-infected NK cells was significantly greater than that of uninfected NK cells. The doubling time of this infected population was reduced from 9 days to 3 days, and the overall survival of the culture in the absence of restimulation was extended from 5 wk to 18 wk. Unlike T lymphocytes, HTLV-I-infected NK cells were not immortal, implying a fundamental difference between these two lymphocyte populations.
Transcription and recombination of the murine RS element.
Authors: Daitch L E , Moore M W , Persiani D M , Durdik J M , Selsing E 
Published: December 2022

Abstract
The deletion of C kappa is a frequent event in lambda-producing B cells in both mice and humans. Deletions of the murine C kappa gene are mediated by recombination events that involve the RS (recombining segment) element located downstream of the C kappa gene. RS recombinations appear to be mediated by the same mechanisms involved in Ig and TCR gene rearrangement. It has been suggested that RS recombinations might activate a factor that is involved in the initiation of lambda gene rearrangement in maturing pre-B cells. We have identified a unique RNA transcript derived from the recombined RS element present in some pre-B cell lines. However, gene transfer studies indicate that this RS transcript is not sufficient to induce lambda gene recombination in pre-B cell lines. We also find that recombination of the RS element in pre-B cell lines is closely correlated with changes in chromatin structure and transcriptional activation. Thus, recombination of the RS element in pre-B cells appears to be regulated in a manner similar to the regulation of antibody gene VDJ joining.
Human leukocyte activation antigen M6, a member of the Ig superfamily, is the species homologue of rat OX-47, mouse basigin, and chicken HT7 molecule.
Authors: Kasinrerk W , Fiebiger E , Stefanová I , Baumruker T , Knapp W , Stockinger H 
Published: December 2022

Abstract
Peripheral granulocytes from rheumatoid arthritis and reactive arthritis patients were recently found to express higher levels of a newly defined Ag, termed M6, in comparison to granulocytes from healthy subjects. We present here the molecular characterization of M6 Ag and show that it is a novel human leukocyte activation-associated cell surface glycoprotein. Peripheral lymphocytes do not significantly express M6 Ag, however, it appears upon 3-day PHA-activated T blasts. On monocytes, which constitutively express M6 Ag, it is down-regulated on day 1 but re-induced on day 3 of granulocyte-macrophage CSF stimulation. SDS-PAGE analysis of M6 immunoprecipitates shows a single band of 54 kDa under nonreducing conditions that shifts to 65 kDa under reducing conditions. Endoglycosidase F treatment of M6 immunoprecipitate reveals that 50% of the M6 molecule is composed of N-linked carbohydrates. By modifying the COS cell cloning strategy, we have isolated cDNA clones encoding M6 Ag. M6 cDNA hybridizes with a single mRNA transcript of approximately 1.7 kb in Northern blotting. Comparison analysis of the M6 sequence indicates that M6 Ag is a member of the Ig superfamily and the species homologue of rat OX-47 Ag, mouse basigin (gp42), and chicken HT7 molecule. The highly conserved remarkable transmembrane domain suggests that the M6 Ag may be a component of a multichain complex in the plasma membrane.
Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis factor-alpha.
Authors: Görgen I , Hartung T , Leist M , Niehörster M , Tiegs G , Uhlig S , Weitzel F , Wendel A 
Published: December 2022

Abstract
Pretreatment with recombinant human granulocyte CSF (G-CSF) protected mice in two different models of septic shock. Intravenous injection of 250 micrograms/kg G-CSF to mice prevented lethality induced by 5 mg/kg LPS. Injection of 50 micrograms/kg G-CSF protected galactosamine-sensitized mice against LPS-induced hepatitis. In either case, this protection was accompanied by a suppression of LPS-induced serum TNF activity. In contrast, when galactosamine-sensitized mice were pretreated with 50 micrograms/kg murine recombinant granulocyte/macrophage CSF instead of G-CSF and subsequently challenged with LPS, serum TNF activity was significantly enhanced and mortality was increased. The suppressive effect of G-CSF on LPS-induced TNF production was also demonstrated in rats. In vivo, no TNF was detectable in the blood of LPS-treated rats, which had been pretreated with G-CSF. Ex vivo, alveolar macrophages, bone marrow macrophages, Kupffer cells, or peritoneal macrophages prepared from G-CSF-treated rats produced significantly less TNF upon stimulation with LPS than corresponding populations from control rats. However, when these macrophage populations were incubated with G-CSF in vitro, LPS-induced TNF production was unaffected. These data suggest that the G-CSF-mediated suppression of TNF production is not a direct effect of G-CSF on macrophages. To examine whether, independent of the protection against LPS, G-CSF treatment still activated neutrophils, it was demonstrated that granulocytes from G-CSF-treated rats were primed for PMA-induced oxidative burst and for ionophore/arachidonic acid-stimulated lipoxygenase product formation. The experiments of this study support the notion that G-CSF is a negative feedback signal for macrophage-derived TNF-alpha production during Gram-negative sepsis.
A kinetic study of immune mediators in the lungs of mice infected with influenza A virus.
Authors: Hennet T , Ziltener H J , Frei K , Peterhans E 
Published: December 2022

Abstract
We investigated a broad spectrum of immunoactive mediators in a mouse model of influenza. ICR mice (4-5 wk old) that were infected with a 10 LD50 dose of influenza A/PR8/34 virus died after 6 days without evidence of bacterial superinfection. Maximal virus titers were reached by day 2 postinfection, whereas the multifocal pneumonia with mononuclear cell infiltration reached its maximum at the end of infection. We measured the cytokines IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-6, IFN-gamma, TNF-alpha, granulocyte (G)/macrophage (M)-CSF, G-CSF, M-CSF, and the lipid mediators leukotriene B4 and platelet-activating factor in the cellfree bronchoalveolar lavage fluid of mice during infection. We found an early increase of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, GM-CSF, IFN-gamma, and leukotriene B4. Levels of these factors peaked between 36 h and day 3 postinfection, with the exception of IL-6 that remained at elevated levels throughout infection. G-CSF and M-CSF increased slowly and reached a maximum by day 5 postinfection. We were unable to detect IL-2, IL-3, or IL-4. PAF remained at the same level throughout infection. Our results suggest that lung-resident cells, and possibly the alveolar macrophages, participate actively in the onset of the inflammatory response against the invading virus. The inability to detect the T cell products IL-2, IL-3, and IL-4 was unexpected considering the role of T cells in the elimination of the virus in infected mice. Our observation confirms thus earlier findings about the inability of specific T cell clones to elicit an unspecific antiviral effect.