bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chymotryptic-type protease inhibitors block the increase in Ca2+ and Il-2 production in activated Jurkat T cells.
Authors: Auberger P , Mary D , Breittmayer J P , Aussel C , Fehlmann M 
Published: December 2022

Abstract
Several chymotryptic-type protease inhibitors were found to inhibit both anti-CD3 mAb- and PHA-induced rise in Ca2+ and IL-2 production in Jurkat T cells. The magnitude of inhibition was a function of the effectors used to stimulate Ca2+ entry and depended on the concentration of the inhibitors. Neither tryptic-type protease inhibitors nor an elastase substrate prevented anti-CD3 mAb- or PHA-induced Ca2+ rise in Jurkat cells. The inhibitory effect of N-alpha-p-tosyl-L-phenylalanine chloromethyl-ketone on anti-CD3 mAb- and PHA-induced rise in Ca2+ resulted from a rapid increase in Ca2+ efflux. The inhibitors which were effective on Ca2+ mobilization also inhibited IL-2 production initiated by an anti-CD3 mAb in the presence of 12-O-tetradecanoylphorbol-13-acetate, and to a lesser extent by PHA or the calcium ionophore A23187. No inhibition of IL-2 production was observed when tryptic-type protease inhibitors or the elastase inhibitor were used. In addition, membrane preparations from Jurkat cells were found to hydrolyze the chymotryptic substrate Suc-Ala-Ala-Phe-paranitroaniline, an effect markedly inhibited by N-alpha-p-tosyl-L-phenylalanine chloromethylketone. Moreover, this inhibitor protected one potential endogenous substrate (Mr 38 kDa) from proteolysis. Taken together, these observations show that chymotryptic-type protease inhibitors block the responses generated by the binding of anti-CD3 mAb to Jurkat cells, and suggest that a chymotryptic-like membrane protease contributes to T cell activation.
Superoxide-dependent nitroblue tetrazolium reduction and expression of cytochrome b-245 components by human tonsillar B lymphocytes and B cell lines.
Authors: Maly F E , Nakamura M , Gauchat J F , Urwyler A , Walker C , Dahinden C A , Cross A R , Jones O T , de Weck A L 
Published: December 2022

Abstract
EBV-transformed B lymphocyte cell lines can generate superoxide, using an electron transport chain homologous, or even identical, to phagocytic NADPH-oxidase. We searched for normal, not virally transformed, B lymphocytes with analogous properties, using tonsils as the source of B cells. Unseparated tonsillar leukocytes contained cells capable of PMA-triggered superoxide dismutase-inhibitable reduction of nitroblue tetrazolium (NBT+ cells) well in excess of phagocytes (18.9 +/- 6.4% NBT+ cells with 1.3 +/- 0.9% granulocytes and 1.9 +/- 2.3% monocytes/macrophages, n = 8). NBT reduction was also inhibited by diphenylene iodonium, a selective inhibitor of phagocytic NADPH-oxidase. Cross-linking of surface Ig was equally effective as PMA in inducing NBT reduction among tonsillar leukocytes. NBT+ cells co-distributed with B cells on Percoll density gradients and were enriched among purified B cells obtained by SRBC rosetting twice and Sephadex G10 adherence (47.8 +/- 15.2% NBT+ cells among 90.5 +/- 5.5% B cells, 4.8 +/- 5.1% T cells, 1.2 +/- 0.77% monocytes/macrophages, and 0.73 +/- 0.6% granulocytes, n = 10). Further, mAb 7D5, directed against an extracellularly located epitope of the small subunit of cytochrome b-245 of phagocytes, stained the majority of tonsillar B cells (85 +/- 9.2% 7D5+ cells and 91.6 +/- 4.04% B cells, n = 3). Superoxide production, staining with 7D5 antibody, and expression of mRNA for the beta chain of cytochrome b-245 were further analyzed in cell lines. The EBV-BLCL F1 and the Burkitt lymphoma P3HR-1 both carried 7D5-detectable cytochrome b-245 Ag and expressed mRNA for the beta chain of the cytochrome b, both in similar amounts. However, only F1, not P3HR-1, was capable of PMA-triggered superoxide production. These data indicate that also normal nontransformed B lymphocytes possess the capacity to generate superoxide by a system apparently similar to phagocytic NADPH-oxidase, provisionally termed "B cell oxidase." Discrepancies observed in certain B cells and lines between expression of cytochrome b components and stimulus-induced superoxide production may be related to an absence or low level of other oxidase components or of the signal transduction mechanism. Conceivably, production of superoxide and derived reactive oxygen species by B cells may have cytotoxic, immunomodulatory, or mutagenic effects on the B cells themselves or on cells in their immediate vicinity.
Experimental and theoretical kinetics study of antibacterial killing mediated by human natural killer cells.
Authors: Garcia-Peñarrubia P , Bankhurst A D , Koster F T 
Published: December 2022

Abstract
We have recently shown that purified human NK cells, both resting and activated, efficiently kill gram-negative and gram-positive bacteria in vitro. To investigate the mechanism of NK cell-mediated cytotoxicity against Escherichia coli we have developed a mathematical model of the kinetics using the experimental data. The kinetics of killing are characterized by initial target bacterial multiplication, followed by rapid bacterial death. Experiments demonstrates that for each donor there is a threshold number of effector cells necessary to observe a net killing effect. Below the threshold, even use of high effector-to-target ratios lack killing activity and the bacterial growth cannot be stopped. In contrast, if the number of NK cells is larger than the threshold, complete killing is achieved, even at ratios as low as 1/1000. The threshold number varies among donors, ranging between 1200 and 12000 purified NK cells/tube, and provides a quantitative measure of antibacterial activity. Performing the assay at 4 degrees C raised the threshold number required for killing. Experiments performed in Boyden chambers confirm that NK cell-bacteria contact is not necessary for efficient killing, although the kinetics of bacterial lysis is slower. The fit between model and data supports the hypothesis that the bactericidal mechanism is extracellular and is mediated by an anti-microbial factor released from NK cells. Accumulated evidence also indicates that this factor is distinguishable from the mechanisms mediating tumor cell cytotoxicity.
Protective immunity in mice vaccinated with the Schistosoma mansoni P-28-1 antigen.
Authors: Wolowczuk I , Auriault C , Gras-Masse H , Vendeville C , Balloul J M , Tartar A , Capron A 
Published: December 2022

Abstract
The P28-1 Ag induces a strong protective immunity toward Schistosoma mansoni infection in various experimental models. T lymphocytes of mice immunized with the recombinant P28-1 Ag were stimulated in vitro by schistosome Ag of different development stages and by three P28-1 Ag-derived synthetic peptides. The most significant stimulation was achieved with the 24-43 peptide. The use of two fragments of this peptide showed that the P28-1 T lymphocyte specificity concerned essentially the NH2 terminal sequence of the 24-43 peptide. Moreover, T lymphocytes specific for the 24-43 peptide were stimulated by both schistosome Ag and the recombinant P28-1 protein. The passive transfer of (Th + Ts) lymphocytes recovered from P28-1 Ag-immunized mice increased the IgG response to P28-1 and its peptides during infection but did not protect against a challenge infection, such as the passive transfer of anti-P28-1 sera. In contrast, P28-1 specific Th cell lines maintained in culture for 2 mo, passively transferred a strong protection (50%) to infected mice. Supernatants of P28-1-specific T cells obtained after stimulation with the corresponding Ag, were able to confer cytotoxic properties to platelets and macrophages. The presence of IFN-gamma for the cytotoxicity mediated by platelets and macrophage activating factor for the cytotoxicity mediated by macrophages in these supernatants is in a large part responsible for the parasite killing observed. Finally, a preliminary immunogenetic approach with H-2 congenic mice on BALB background showed that the P28-1 Ag T cell response was under the control of the MHC and that the H-2b haplotype determined a low response to P28-1 Ag and its peptides while H-2d and k haplotypes determined high responders.
Antigen presentation abrogated in cells expressing truncated Ia molecules.
Authors: Nabavi N , Ghogawala Z , Myer A , Griffith I J , Wade W F , Chen Z Z , McKean D J , Glimcher L H 
Published: December 2022

Abstract
Oligonucleotide site-directed mutagenesis was used to introduce a premature stop codon in wildtype A beta k and A alpha k cDNA clones to create truncated A beta k and A alpha k molecules lacking the cytoplasmic domain. Transfected B lymphoma cells expressing an I-Ak molecule with a truncated beta-chain or with truncated alpha- and beta-chains showed profound defects in two Ia-related functions: Ia-restricted Ag presentation and intracytoplasmic signaling. The ability of these transfected cell lines to activate autoreactive T hybrids was markedly impaired whereas loss of Ag presentation to nominal Ag-specific T hybrids was more subtle. Ia-mediated transmembrane signaling as measured by PKC translocation from cytosol to nucleus after stimulation with anti-Ak antibody was greatly affected by truncation of the A beta and A alpha cytoplasmic domains. These results indicate an important role for the highly conserved cytoplasmic domain in Ia-mediated responses.
The role of mast cells in the elicitation of experimental allergic encephalomyelitis.
Authors: Dietsch G N , Hinrichs D J 
Published: December 2022

Abstract
Experimental allergic encephalomyelitis (EAE), a T cell-mediated autoimmune disease can be transferred with lymphoid cells from actively immunized rats into naive recipients. In the mouse, previous studies have suggested a role for histamine/serotonin in the development of active EAE. We have found that myelin basic protein-reactive cells transfer a biphasic skin test response to naive rats analogous to what has been described in the mouse contact dermatitis system, where mast cell sensitization by Ag-specific T cell factors is required for the induction of skin test responses. Treatment of cell recipients with the serotonin receptor antagonists, cyproheptadine or methysergide, blocked or significantly reduced the development of EAE. Furthermore, it was found that treatment with cyproheptadine was effective in blocking clinical disease when administered day 3 to day 6 after cell transfer. In contrast, cyproheptadine treatments before induction of paralysis day 0 to 3, failed to alter the course of clinical disease. The inhibitor of mast cell degranulation, proxicromil, was also found to effectively block the elicitation of adoptively transferred EAE and was also found to be effective when administered just before the onset of clinical disease. Reserpine, a compound known to deplete mast cells of vasoactive amines by forcing granule contents into the cytoplasm where they are degraded by cell enzymes, was also effective in blocking both active and adoptively transferred EAE. Disease inhibition was found to be partially reversed with pargyline, an inhibitor of monoamine oxidase. In addition lymphocytes from treated animals were capable of transferring disease to naive recipients and appeared to have normal activity as assessed by Ag-or mitogen-driven proliferation in addition to IL-2 production.
Modulation of F1 cytotoxic potentials by graft-vs-host reaction. Cooperative non-H-2- and H-2D region-gene control of F1 natural resistance to graft-vs-host reaction-associated immunosuppression.
Authors: Ishikawa H , Saito K , Kubota E 
Published: December 2022

Abstract
Our previous study revealed that in F1 mice raised by crossing C3H/He or AKR/J mice with various H-2-congenic B10-series strains, parental H-2k spleen cells (SC) could not induce the graft-vs-host reaction (GvHR)-associated immunosuppression (GAIS). We also elucidated that a limited number of non-H-2 genes of parental C3H/He or AKR/J mice that had been incorporated into the F1 hybrids determined the F1 resistance to the GAIS, and the present study was done to explore the mechanism implicated in this type of F1 resistance to GAIS. SC from B10.AL mice carrying an rH-2 (K:k I:k S:k D:d) haplotype but not SC from H-2K B10.BR (k k k k) mice induced GAIS of in vitro CTL responses to third-party alloantigens in H-2k/d (C3H/He x B10.D2)F1 recipients mice. Further, SC from H-2k/a (C3H/He x B10.A)F1 mice carrying heterozygous C3H/B10 non-H-2 background but not SC from the same H-2k/a (B10.BR x B10.A)F1 mice but carrying homozygous B10/B10 background induced GAIS in H-2k/d (C3H/He x B10.D2)F1 recipients. Although C3H/He-, B10.BR-, and C3H.OH (d d d k)-SC were incapable of inducing GAIS in (C3H/He x B10.D2)F1 (k/d k/d k/d k/d) recipients, they were all good inducers of GAIS in (C3H.OH x B10.BR)F1 (d/k d/k d/k k/k) recipients. Exactly the same pattern of co-operative non-H-2 AKR and H-2D region-gene control of GAIS was observed on GvHR induced in H-2k/d (AKR/J x B10.D2)F1 recipients. These results suggest that the non-H-2 genes of C3H/He or AKR/J strain inhibit the functional expression of certain antigenic determinant(s) when it is encoded by heterozygous but not homozygous gene(s) linked tightly to H-2D region of k haplotype. Thus, the F1 resistance to GAIS is mediated by immune response of F1 recipients who miss the antigenic determinant(s) against that expressed on cell surface of GvHR-inducing T lymphocytes.
Complement-mediated inhibition of function in complement-resistant Escherichia coli.
Authors: Dankert J R 
Published: December 2022

Abstract
C-mediated inhibition of function in C-sensitive strains of Escherichia coli involves the assembly of the membrane attack complex (MAC) on the outer membrane with subsequent inhibition of inner membrane function. The inhibition of inner membrane function is critical for effective cell killing as damage to the outer membrane alone is insufficient to kill a cell in the absence of serum lysozyme. Studies on the measurement of oxygen consumption for cells under complement attack showed that C-sensitive cells were inhibited by assembly of the MAC, and that this represents damage to some component of the respiring inner membrane. Mechanisms of cellular resistance to C attack could include 1) inhibition of the assembly of the MAC, 2) inhibition of effective activation of the assembled MAC, or 3) reversal of the inhibitory effects of the MAC. Demonstration of a transient C-mediated inhibition of inner membrane function in C-resistant cells implies that the latter case should be considered as one possible component of cellular resistance to C attack.
Intracellular cleavage of newly synthesized low affinity Fc epsilon receptor (Fc epsilon R2) provides a second pathway for the generation of the 28-kDa soluble Fc epsilon R2 fragment.
Authors: Lee B W , Simmons C F , Wileman T , Geha R S 
Published: December 2022

Abstract
It has been reported that the 45-kDa low affinity Fc epsilon R (Fc epsilon R2) on B cells is cleaved spontaneously from the cell surface to release a 28-kDa soluble fragment (sFc epsilon R2). This study demonstrates an additional mechanism by which B cells generate this fragment. Data from 35S methionine pulse-chase experiments with the Fc epsilon R2 bearing human B lymphoblastoid cell line, RPMI 8866, and immunoprecipitations of cell lysates and culture supernatants with an Fc epsilon R2 specific mAb, mAb 25, demonstrates the existence of a cell-associated 28-kDa Fc epsilon R2 fragment. This fragment was shown by partial amino(NH2)-terminal sequence analysis to be identical to the previously described 28-kDa sFc epsilon R2. The resistance to cell treatment with trypsin indicated that it was located intracellularly. Its appearance early in the biosynthesis of the Fc epsilon R2 (within a 10-min pulse), before the Fc epsilon R2 reached the cell surface, suggested that some of this fragment was generated intracellularly. Neutralization of acidic organelles with NH4Cl inhibited the formation of this intracellular fragment, strongly suggesting that it was a produce of intracellular cleavage of the Fc epsilon R2. Finally, this 28-kDa intracellular fragment was shown to be released into the culture supernatant, suggesting an intracellular mechanism by which the cells generate sFc epsilon R2.
Evidence that a kinase distinct from protein kinase C induces CD3 gamma-subunit phosphorylation without a concomitant down-regulation in CD3 antigen expression.
Authors: Cantrell D A , Friedrich B , Davies A A , Gullberg M , Crumpton M J 
Published: December 2022

Abstract
An immediate consequence of Ag-specific activation of T cells is phosphorylation of the gamma-subunit of the CD3 gamma-chain. There is good evidence that the kinase that mediates CD3 gamma-chain phosphorylation is protein kinase C (pkC). It has also been proposed that the interaction between pkC and CD3 gamma-chains controls the cell surface expression of the antigen receptor/CD3 Ag complex. In the present study we present data relevant to these two points. Thus we show that CD3 gamma-subunit phosphorylation can be triggered by the calcium ionophore ionomycin. However, as judged by several criteria, ionomycin does not stimulate cellular pkC. Accordingly, ionomycin must regulate phosphorylation of the CD3 Ag by a kinase distinct from pkC. The phosphorylation of CD3 Ag induced by ionomycin is not accompanied by a modulation of the cell surface expression of CD3 molecules which implies that CD3 gamma-chain phosphorylation is not a sufficient signal for the endocytosis of the CD3/Ag receptor complex.
Characterization of a protein from Trypanosoma cruzi trypomastigotes that cleaves non-immune IgG bound through its Fab fragment.
Authors: Cicarelli R M , Lopes J D 
Published: December 2022

Abstract
A protein from Trypanosoma cruzi bloodstream trypomastigotes that binds IgG from man and several other animal species was isolated and characterized. The 52-kDa protein obtained from different T. cruzi cell extracts showed saturable binding with a K of 3.72 nM. Immunoblot analysis revealed that Fab, but not Fc, fragments of the Ig were recognized. When the protein was added to an unrelated C-fixation reaction, lysis was abolished in a dose-dependent fashion. When freshly prepared T. cruzi extracts were run in a 10% acrylamide SDS gel into which normal rabbit IgG was incorporated before polymerization, proteolytic activity, as seen by a transparent band after Coomassie blue staining, migrated in the same m.w. range of the 52-kDa protein. These data provide further clues to the mechanisms through which this pathogen escapes the host's immune response, thus maintaining a long-standing infection.
Trypanosoma musculi co-express several receptors binding rodent IgM, IgE, and IgG subclasses.
Authors: Vincendeau P , Daëron M 
Published: December 2022

Abstract
The present work demonstrates the expression of receptors for the Fc portion of rodent Ig by the murine parasite Trypanosoma musculi. By using a rosette assay adapted to the parasite morphology and by flow cytometry analysis, three distinct receptors were identified. A receptor binding rabbit or rat polyclonal IgG and mouse monoclonal IgG1, IgG2a, and IgG2b was found on parasites purified from the blood and the peritoneal cavity of infected mice and on parasites maintained in culture conditions. This IgG receptor was degraded by pepsin. A separate receptor, binding only mouse monoclonal IgG3 was observed on cultured parasites. A receptor binding rabbit, rat, and mouse IgM was found on cultured and peritoneal parasites, but not on blood parasites. This receptor did not bind IgG or IgA but it bound mouse and rat IgE as well as IgM. It was degraded by trypsin. IgG and IgM/IgE receptors were co-expressed on single parasites. They were not of host origin but synthesized by trypanosomes as shown by reexpression in vitro after proteolytic degradation. Their expression was variable with the development of trypanosomes both in vitro and in vivo.
Virus-induced polyclonal cytotoxic T lymphocyte stimulation.
Authors: Yang H Y , Dundon P L , Nahill S R , Welsh R M 
Published: December 2022

Abstract
Infections with a variety of viruses (lymphocytic choriomeningitis (LCMV), murine cytomegalovirus, Pichinde virus, vaccinia virus) stimulated C57BL/6 mice to generate allospecific CTL coincidental with the generation of virus-specific CTL. In C57BL/6 (H-2b) mice, LCMV-induced CTL with reactivity against cells from mice bearing gene products of the d, f, k, p, q, and s but not the b MHC loci. Studies with congenic mouse strains indicated that the MHC loci coded for the target of the allospecific killer cells. The targets of the allospecific CTL were further identified as class I MHC Ag by three criteria: 1) target cells from congenic strains of mice differing from effector cells only in the expression of class I Ag were sensitive to lysis; 2) fibroblasts expressing low levels of class I Ag were resistant to lysis but were rendered sensitive after treatment with IFN-beta, which induced higher expression of class I Ag; and 3) antibody specific for class I Ag expressed on the target cell blocked killing. Studies with congenic mouse strains also suggested that the ability to generate high levels of the virus-induced allospecific killer cells was also under MHC regulation, as H-2b mice generated high levels and H-2k mice low levels of the allospecific CTL. Both C3H/St and C57BL/6 mice immunized against LCMV developed detectable LCMV-specific CTL when later challenged with either murine cytomegalovirus, Pichinde virus, or vaccinia virus, indicating that a virus infection can stimulate the reappearance of memory CTL. Cold target competition studies indicated no cross-reactivities between these viruses or allogeneic cells at the CTL level. Both the allospecific CTL and the reactivated LCMV-specific CTL were found in blast-size lymphocyte preparations. Spleen cells taken from LCMV-infected C57BL/6 mice 5 days post-infection spontaneously generated into allospecific and virus-specific CTL after 2 days of culture. The generation of both was dependent on the presence of supernatant factors produced only in the presence of L3T4+ cells. These factors activated allospecific CTL in spleen cells from virus-primed mice but not from control mice. We suggest that lymphokines produced as a consequence of virus infection may act to stimulate the proliferation and activation of CTL not specific to the challenge virus, resulting in a virus-induced polyclonal CTL stimulation.