bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat shock enhances antigen processing and accelerates the formation of compact class II alpha beta dimers.
Authors: Cristau B , Schafer P H , Pierce S K 
Published: December 2022

Abstract
The heat shock response is a universal and highly conserved cellular response to stress. Here we describe the effect of heat shock induced by elevated temperatures on the processing and presentation of an exogenous Ag, cytochrome c, to an Ag-specific class II-restricted T cell hybrid. Heat shock markedly enhances processing of Ag entering the B cell either through fluid phase pinocytosis or through receptor-mediated endocytosis. B cells undergoing a stress response require less time to process and present Ag and achieve higher levels of T cell activation as compared with control cells. Augmented processing and presentation requires that the Ag be present during the stress response. Heat shock has no effect on the presenting ability of B cells that had already processed Ag; and heat shock in the absence of Ag has little effect on subsequent processing or presentation of Ag. Heat shock has no measurable effect on the cell surface expression of class II as measured by flow cytometry but markedly accelerates the formation of compact alpha beta dimers in B cells. The class II purified from heat shocked cells is more active in Ag presentation assays in vitro as compared with class II purified from cells grown at 37 degrees C, indicating that class II formed during a stress response is not identical to that formed under normal conditions. The effect of heat shock on B cell Ag processing reported here is likely to be relevant to processing in vivo, which may often proceed under conditions that induce the heat shock response, such as during viral or bacterial infections, inflammation, and fever.
Cellular basis of differential responsiveness of lymph nodes and spleen to 23-valent Pnu-Imune vaccine.
Authors: Garg M , Kaplan A M , Bondada S 
Published: December 2022

Abstract
Subcutaneous administration with 23-valent pneumococcal polysaccharide vaccine (Pnu-Imune) elicited a good antipneumococcal capsular polysaccharide response from the spleen but not from peripheral lymph nodes (LN) (cervical, brachial, axillary, popliteal, inguinal) of BALB/c mice. To evaluate the cellular basis of the unresponsiveness of LN to this vaccine and to identify the cell types in spleen that are necessary for induction of polysaccharide Ab responses, a reliable in vitro culture system was developed to obtain plaque-forming cell responses to the Pnu-Imune vaccine. The in vitro antipneumococcal polysaccharide response of mouse spleen cells was found to be relatively T cell independent. Unlike spleen cells, LN cells did not respond to the Pnu-Imune vaccine in vitro. However, LN cells responded to Pnu-Imune vaccine when co-cultured with irradiated spleen cells or splenic dendritic cells but not with accessory cell-depleted spleen cells. LN cells were found to contain the necessary accessory cells that can support the polysaccharide response but in reduced numbers. The LN response to the vaccine was also reconstituted by IL-1 or Th2-associated cytokine IL-5. In contrast, IFN-gamma, a Th1 cell-derived lymphokine was able to suppress the in vitro splenic response to the vaccine suggesting that differential activation of Th1 and Th2 types of Th cells might be one mechanism by which T cells regulate Ab responses to pneumococcal polysaccharides.
Resistance to natural killer cell lysis conferred by TAP1/2 genes in human antigen-processing mutant cells.
Authors: Salcedo M , Momburg F , Hämmerling G J , Ljunggren H G 
Published: December 2022

Abstract
The human Ag-processing-defective cell line 721.174, and its derivative T2, have a large homozygous deletion in the MHC class II region encompassing the TAP1 and TAP2 as well as the LMP2 and LMP7 genes. A similar, but smaller defect encompassing the TAP1 gene is observed in the 721.134 mutant cell line. With a few recent exceptions, these lines are unable to present endogenous Ag to class I-restricted CD8+ CTL. However, restoration of Ag processing and presentation to CD8+ cytotoxic T cells can be achieved by transfecting TAP1 and TAP2 genes into the T2 and .174 cells, or the TAP1 gene into .134 cells. In contrast to their resistance to MHC class I-restricted CTL-mediated lysis, T2 and .174 as well as .134 cells are highly sensitive to lysis by human NK cells. In the present study, we demonstrate the reversal of the NK-sensitive phenotype of these mutant cell lines upon transfection of TAP genes. The induced NK cell-resistant phenotype, studied in detail with TAP1/2-transfected T2 cells, appeared independent of the MHC class I haplotype of the NK cell donors and was also observed with xenogeneic NK cells. The resistance to NK cell lysis induced by re-expression of TAP1/2 seemed to be independent of the origin of the TAP genes; both human and rat transporters efficiently conferred NK cell resistance. Transfection of single TAP genes to T2 or .174 cells, whether TAP1 or TAP2, did not markedly affect NK cell susceptibility. This indicates that an intact TAP1/2 dimer, and thus efficient peptide translocation into the ER, is necessary for rendering T2 and .174, as well as .134 cells, resistant to NK cell-mediated lysis. Proper translocation of peptides across the ER membrane and loading to class I molecules may represent critical events in rendering an NK-resistant phenotype.
Distinct pathways of B cell differentiation. I. Residual T cells in athymic mice support the development of splenic germinal centers and B cell memory without an induction of antibody.
Authors: Stedra J , Cerny J 
Published: December 2022

Abstract
B cell memory to T cell-dependent Ags develops in the germinal centers (GC). Here we report that thymus-deficient, nu/nu mice immunized with phosphorylcholine coupled to keyhole limpet hemocyanin (EPC-KLH) develop GC in the spleen in the absence of Ab-forming cell (AFC) response. However, the formation of GC on EPC-KLH immunization requires T cells, because 1) CB.1.7-scid mice reconstituted with B lymphocytes failed to develop GC without a supplement of CD4+ cells and 2) in vivo administration of an anti-CD4 mAb abolished the GC response in euthymic mice. Thus, it appears that the formation of GC in nu/nu mice was due to a low number of T cells that were detectable in situ within the splenic lymphoid follicles. The numbers of GC in individual Ag-stimulated nu/nu mice appeared to correlate with the density of T cells in the splenic sections. The B cells in these GC expressed T15, the dominant Id of anti-PC Ab, and became primed for an anamnestic response. Secondary challenge with EPC-KLH resulted in an increased number of GC without detectable AFC. However, when the Ag-primed nu/nu mice received CD4+ lymphocytes 1 day before the challenge, they demonstrated a vigorous AFC response that was predominantly IgM and significantly higher than the secondary response of nu/nu mice that had been reconstituted with CD4+ cells during both primary and secondary immunizations. Therefore, it appears that immunization of nu/nu mice may lead to an early step of B cell activation and memory development even though the T lymphocytes in these mice are incompetent to provide help for Ab formation. The memory and Ab pathways of B cell differentiation may involve different mechanisms of T cell help.
Migration of so-called naive and memory T lymphocytes from blood to lymph in the rat. The influence of IFN-gamma on the circulation pattern.
Authors: Westermann J , Persin S , Matyas J , van der Meide P , Pabst R 
Published: December 2022

Abstract
It has been suggested that naive T lymphocytes migrate directly from the blood into the lymph nodes, whereas memory T lymphocytes arrive via the afferent lymphatics. However, these routes were defined indirectly by determining only the frequencies of naive and memory T lymphocytes in the afferent and efferent lymph of sheep. In this study naive (CD45RC+) and memory (CD45RC-) CD4+ lymphocytes obtained by thoracic duct cannulation of the rat were injected i.v. and their reappearance in the thoracic duct lymph (efferent lymph) was monitored in absolute numbers over 5 days. In addition, it was investigated whether continuous application of IFN-gamma influences the migration of the two subsets differently. After i.v. injection both naive and memory T lymphocytes returned to the thoracic duct in considerable numbers and with similar kinetic patterns. Interestingly, within 5 days at least 25% of memory phenotype lymphocytes converted to naive phenotype lymphocytes. When naive and memory T lymphocytes were injected in animals receiving a continuous IFN-gamma infusion, only the reappearance of the naive T lymphocytes but not that of memory T lymphocytes in the thoracic duct lymph was reduced. Thus, by investigating the migration of labeled lymphocytes, data were obtained that contradict conclusions drawn by analyzing preferential accumulation of lymphocyte subsets only. Our results suggest that in unstimulated animals naive and memory thoracic duct lymphocytes migrate at a similar tempo and to a comparable extent from the blood via the lymph node into the efferent lymph. IFN-gamma only influences the traffic of naive lymphocytes, indicating that the migration of the two populations is regulated by different mechanisms.
Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways.
Authors: Wong G H , Goeddel D V 
Published: December 2022

Abstract
The Fas Ag and the p55 TNF receptor (TNF-R1) are related molecules that can signal apoptosis. Some tumor cell lines are selectively killed by Fas activation and others by TNF-R1 activation even though both receptors are often co-expressed. TNF-R1-mediated cytotoxicity can be selectively inhibited under conditions in which Fas-mediated cell death is not affected. Activation of both receptors results in synergistic signaling of apoptosis. These results indicate that different biochemical pathways are activated by Fas and TNF-R1. Combination treatment with agonists of Fas and TNF-R1 may have therapeutic potential.
The cloning of CD70 and its identification as the ligand for CD27.
Authors: Bowman M R , Crimmins M A , Yetz-Aldape J , Kriz R , Kelleher K , Herrmann S 
Published: December 2022

Abstract
CD70 is a surface Ag found on activated but not resting T and B lymphocytes. The biologic activity of this Ab-defined cell surface molecule on lymphocytes has not been established. Therefore, in an effort to understand the function of the CD70 protein, a mAb defining the CD70 Ag was used to isolate by expression cloning the cDNA responsible for the CD70 molecule. The predicted protein product is a type II transmembrane protein. Bioassays demonstrated that the CD70 cDNA clone expressed in African green monkey kidney cells would induce the proliferation of PHA-costimulated T cells. Comparison with known sequences indicates identity with the CD27 ligand. Therefore the molecule defining the CD70 Ag is identical to the recently defined ligand for CD27.
Antigen-specific CD8+ T cell clone protects against acute Toxoplasma gondii infection in mice.
Authors: Khan I A , Ely K H , Kasper L H 
Published: December 2022

Abstract
Encephalitis caused by the obligate intracellular protozoan, Toxoplasma gondii, is a major cause of morbidity and mortality in those afflicted with AIDS. The cell-mediated response is critical for host immunity against this parasite. A panel of T cell clones that proliferate in response to a major parasite protein, p30 (SAG-1) were isolated from mice. One of these clones (C3) bearing the CD8+ phenotype was able to induce nearly 100% protection against acute infection when adoptively transferred into naive mice. In contrast, an Ag-specific CD4+ T cell clone (C2) failed to show significant protection in spite of its ability to produce similar quantities of IFN-gamma. Depletion of host CD4+ T cells with mAb had no effect on CD8(+)-mediated adoptive protection, whereas treatment with anti-IFN-gamma completely abrogated this protection. These results indicate that Ag-specific CD8+ T cells in combination with IFN-gamma are able to induce significant protection against acute toxoplasmosis in the experimental murine model.
Acute inflammatory activity of the S100 protein CP-10. Activation of neutrophils in vivo and in vitro.
Authors: Devery J M , King N J , Geczy C L 
Published: December 2022

Abstract
The murine S100 chemotactic protein of m.w. 10,000 termed (CP-10), has potent chemotactic activity for murine and human myeloid cells. We examined the ability of a synthetic CP-10 hinge region peptide CP-10(42-55) and rCP-10 to act as chemotactic agents and induce expression of the adhesion molecule Mac-1 (CD 11b/CD 18) in vivo. Maximal neutrophil (PMN) accumulation occurred between 2 to 8 h after mouse footpad injection of rCP-10 (10(-7) M) or CP-10 peptide (10(-6) M). The infiltrating PMN expressed high levels of Mac-1, and low levels of the murine L-selectin Mel-14. Injection of CP-10 peptide i.p. also induced infiltration of PMNs that expressed high levels of Mac-1. Cell suspensions obtained after i.p. injection of CP-10 peptide could be significantly inhibited from adhering to fibrinogen-coated plates when incubated with anti-Mac-1 antibody. The chemotactic activity of CP-10 peptide toward murine inflammatory PMN in vitro was also inhibited by anti-Mac-1 antibody. Neither CP-10 analogue stimulated or primed murine inflammatory or human blood neutrophils for superoxide production or granular enzyme release. The localization of CP-10 in vivo was examined using murine footpads injected with LPS and was found to be concentrated around the endothelial cells of the small blood vessels. This distribution suggests that the accumulated CP-10 the may contribute to the generation of a chemotactic gradient.
Properties of protein kinase C isoforms (beta II, epsilon, and zeta) in a macrophage cell line (J774) and their roles in LPS-induced nitric oxide production.
Authors: Fujihara M , Connolly N , Ito N , Suzuki T 
Published: December 2022

Abstract
Northern analysis of poly(A)+ RNA extracted from J774 cells (a mouse macrophage cell line) showed that this cell line constitutively expresses mRNAs specific for protein kinase C (PKC)-beta I, -beta II, -epsilon and -zeta, but not those for PKC-alpha, -gamma or -delta. Western analysis of the total cell lysate showed that J774 cells express PKC-beta II, -epsilon and -zeta isoenzymes, but failed to show the expression of PKC-beta I. The exposure of J774 cells to &gt; 10 nM PMA led to a loss of immunoreactive PKC-beta II in 4 h. The down-regulation of immunoreactive PKC-epsilon required more than 8 h of the exposure to &gt; 100 nM PMA. Immunoreactive PKC-zeta was most resistant to PMA treatment and was not significantly reduced after the exposure to 300 to 600 nM PMA for 24 h. PMA-mediated, persistent down-regulation of PKC-beta II is probably a result of the inhibition of PKC-beta II biosynthesis at the posttranscriptional level, because PMA-exposed cells were found to gradually increase the expression of PKC-beta II specific mRNA. PMA-pretreated cells responded to a low dose (10 ng/ml), but not to a high dose (1 microgram/ml), of LPS by significantly lower expression of mRNA specific for the inducible nitric oxide synthase (i-NOS) gene and production of nitric oxide (NO) than the control cells did. Thus, PKC could be a part of the signal transduction apparatus involved in LPS-induced inducible nitric oxide synthase gene activation.
Deletion and editing of B cells that express antibodies to DNA.
Authors: Chen C , Radic M Z , Erikson J , Camper S A , Litwin S , Hardy R R , Weigert M 
Published: December 2022

Abstract
We previously demonstrated that in mice transgenic for genes coding for an anti-ssDNA autoantibody B cells were functionally inactivated but not physically deleted. We have now extended this model by introducing an arginine into the CDR2 of the heavy chain transgene. This change alters the specificity of the Ab from anti-ssDNA to anti-dsDNA and increases the affinity for ssDNA. Mice carrying this transgene displayed a significant reduction of peripheral B cells and anti-dsDNA B cells were not recovered from the spleens. The remaining B cells escape deletion by revising their Ag receptors in several ways: 1) elimination of the transgenic heavy chain gene via intrachromosomal recombination, followed by rearrangement and expression of endogenous VH genes; 2) ongoing rearrangement of endogenous kappa light chain genes to generate a non-dsDNA-binding Ab; and 3) expression of a rare V lambda gene, V lambda x, to generate a non-DNA-binding Ab.
Development and characterization of channel catfish long term B cell lines.
Authors: Miller N W , Rycyzyn M A , Wilson M R , Warr G W , Naftel J P , Clem L W 
Published: December 2022

Abstract
The establishment of channel catfish long term cloned B cell lines, the first such cell lines from ectothermic vertebrates, is described. These diploid cell lines were developed by in vitro LPS stimulation of B cells from normal channel catfish peripheral blood in the absence of overt attempts to transform or immortalize the cells. The resultant cell lines were cloned and maintained continuously in vitro for more than 12 mo without restimulation, feeder cells, or exogenous factors. Southern blot analyses of the parental cell lines revealed multiple mu-chain gene rearrangements, suggesting a polyclonal origin for the cell lines. Additional evidence for polyclonal development was provided by the demonstration that the parental cell lines transcribed mRNA for all of the six known channel catfish VH gene families. The characterization of several clonal cell lines revealed mRNA expression for both the secreted and membrane forms of the catfish mu-chain; however, the cloned cell lines each expressed only a single VH gene and analysis of the Ig H chain locus was consistent with allelic exclusion having occurred in these cells. Flow cytometry demonstrated that the cloned and uncloned cell lines produced both cytoplasmic and cell surface IgM. This IgM contained only one of the two L chain isotypes of the channel catfish, suggesting preferential L chain usage. Although these cells did not appear morphologically to be plasma cells, they secreted moderate levels of IgM in culture. These cell lines have considerable potential for addressing questions concerning the evolution of B cell function.
MTS-32 monoclonal antibody defines CD4+8- thymocyte subsets that differ in their maturation level, lymphokine secretion, and selection patterns.
Authors: Vicari A , Abehsira-Amar O , Papiernik M , Boyd R L , Tucek C L 
Published: December 2022

Abstract
We have previously described MTS-32 as identifying an Ag on both thymic stromal cells and thymocytes. In contrast with CD4+8+ and CD4-8+ thymocytes, of which the vast majority are MTS-32+, a notable subset of CD4+8- thymocytes is MTS-32-. Here we show that with regard to heat-stable Ags, Qa-2, and CD69 expression CD4+8- MTS-32- thymocytes are phenotypically enriched in mature cells when compared with their MTS-32+ counterparts. Moreover, sorted CD4+8- MTS-32+ thymocytes are unable to respond to anti-CD3 cross-linking, whereas MTS-32- CD4+8- thymocytes respond to the same stimulus by producing IL-4, IL-5, IL-10, IFN-gamma, and trace amounts of IL-2. In addition, MTS-32- CD4+8- and CD4-8- TCR-alpha beta+ thymocytes differ in their TCR V beta repertoire on a Mls-1a selecting background. We therefore suggest that the MTS-32 ligand is involved in signals consecutive with TCR recognition in the thymus, i.e., selection, activation, and lymphokine production.
Role of infused CD8+ cells in the induction of peripheral tolerance.
Authors: Zhang L , Shannon J , Sheldon J , Teh H S , Mak T W , Miller R G 
Published: December 2022

Abstract
The CD8 molecule when present on a cell recognized by a mature T cell has been shown to have an inhibitory effect on the development of an in vitro immune response by that T cell. To test whether CD8 has a role in the induction of peripheral tolerance in vivo, we have studied tolerance induction in B6 female mice carrying a transgenic TCR specific to male H-Y Ag. Previous studies have shown that male Ag reactive cells are inactivated in these mice after the i.v. injection of viable male lymphoid cells. Here, B6 female transgenic mice were injected with B6 male lymph node cells from CD4 or CD8 gene knockout mice, and the fate of male Ag-specific T cells was followed in vivo. Our results indicate that injection of male CD4 knockout (express CD8) lymphoid cells but not CD8 knockout (do not express CD8) lymphoid cells induced a significant reduction of male H-Y Ag reactive cells in the periphery, suggesting that CD8 plays an important role in the induction of peripheral tolerance of class I-restricted T cells. These results imply that peripheral tolerance can be induced not just by absence of signals required for activation but by the presence of additional signals.
Regulation of IFN-gamma-induced nuclear expression of IFN consensus sequence binding protein in murine peritoneal macrophages.
Authors: Politis A D , Ozato K , Coligan J E , Vogel S N 
Published: December 2022

Abstract
IFNs are well characterized macrophage-activating agents. Their varied effects are largely mediated via the induction of many genes, whose products act in concert to induce macrophage differentiation. Homologous DNA sequences have been found upstream of the promoter in many of these IFN-inducible genes and bind a family of trans-acting proteins. Interferon consensus sequence binding protein (ICSBP) is one member of this family of interferon regulatory factors (IRF) and is structurally related within the DNA-binding domain to the other members, IRF-1, IRF-2, and ISGF3 gamma. ISCBP mRNA levels become elevated in response to IFN-gamma; however, little is known about the regulation of ICSBP expression at the protein level. In this study, anti-ICSBP peptide Abs were used to quantify and localize ICSBP in murine peritoneal exudate macrophages. Western blot analysis of cytoplasmic and nuclear extracts from treated and control cells revealed ICSBP to be induced by IFN-gamma and not by IFN-alpha and to exist primarily in the nucleus. The regulation of ICSBP induction by IFN-gamma was consistent with the characteristics found at the mRNA level; inhibition by IFN-alpha or glucocorticoids and the requirement for protein kinase C (as determined pharmacologically). The time course of IFN-gamma-induced ICSBP showed an induction of protein that required approximately 12 h to reach maximal levels. Induced ICSBP was relatively stable, exhibiting a half-life of approximately 48 h. Indirect immunofluorescence also demonstrated ICSBP to be an IFN-gamma-inducible protein that is strongly localized to the nucleus.