bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon-gamma induction by lipopolysaccharide: dependence on interleukin 2 and macrophages.
Authors: Blanchard D K , Djeu J Y , Klein T W , Friedman H , Stewart W E 
Published: December 2022

Abstract
Bacterial lipopolysaccharide (LPS) induced fresh murine splenocytes to produce interferon (IFN)-alpha/beta presumably by stimulation of the B lymphocytes and macrophages. However, when the splenocytes were "aged" for 24 to 72 hr in culture before addition of the LPS, the IFN response was significantly increased and was determined to be predominantly IFN-gamma. Because low levels of interleukin 2 (IL 2) were found to be spontaneously produced by the unstimulated splenocytes during the "aging" process, the effect of IL 2 on IFN induction by LPS in fresh splenocytes was examined. The addition of LPS to freshly prepared splenocyte cultures that were treated with human IL 2, either native or recombinant, before exposure to the LPS resulted in the LPS inducing large amounts of IFN-gamma. IL 2 alone induced little if any IFN in the splenocyte cultures. Depletion of T cells and large granular lymphocytes (LGL) from the cultures by anti-Thy-1.2 antibodies plus complement abrogated IFN-gamma production, and the addition of polymyxin B to "aged" splenocyte cultures resulted in loss of IFN production in response to LPS. Cultures that were enriched for T cells and LGL by passage through nylon wool produced significant amounts of IFN-gamma in response to LPS only if first treated with IL 2. Furthermore, the addition of splenic adherent cells to purified nylon wool-non-adherent (NWNA) cells augmented IFN-gamma production, whether or not the NWNA cells were pretreated with IL 2. This enhancement appeared to require direct contact between adherent cells and NWNA cells, because physical separation abrogated IFN production. The addition of recombinant IL 1 or LPS-conditioned supernatants of macrophage cultures did not replace adherent cell activity. These data demonstrate that LPS, which predominantly induces IFN-alpha/beta in fresh murine splenocytes, is able to stimulate T lymphocytes to produce IFN-gamma if the T cells are first exposed to endogenously produced or exogenously applied IL 2. Because IFN-gamma is a potent activator of the bactericidal and cytocidal potential of macrophages, the induction of IFN-gamma by bacterial LPS may play an important role in resistance/recovery mechanisms against bacterial infections.
Expression of interleukin 2 receptors on interleukin 3-dependent cell lines.
Authors: Koyasu S , Yodoi J , Nikaido T , Tagaya Y , Taniguchi Y , Honjo T , Yahara I 
Published: December 2022

Abstract
Several mouse IL 3-dependent cell lines, IC2, LT4, FDC-P2, and PB-3C, derived from spleen or bone marrow cells were shown to express low affinity receptors for IL 2 (Kd; 0.5 to 8 X 10(-8) M). High affinity receptors for IL 2 were not detected on the IL 3-dependent cells within the experimental limitation of this study. The clones did not respond to IL 2 at all at the concentration as high as 25 micrograms/ml. The number of the receptors expressed on those clones was estimated to be 0.2 to 2 X 10(5)/cell, which is comparable with the number of those on IL 2-dependent T cell clones. Expression of IL 2 receptor was confirmed in mRNA levels for both IC2 and LT4 cells. A relatively low level expression of one (4.5 Kb) of four IL 2 receptor mRNA species was observed with those IL 3-dependent clones compared with IL 2-dependent T cells. It seems that these low affinity receptors may be expressed on IL 3-dependent cells that undergo differentiation or maturation in mast cell and some myeloid cell lineages.
Regulation of immunoglobulin synthesis by human T cell subsets as defined by anti-D44 monoclonal antibody within the CD4+ and CD8+ subpopulations.
Authors: Calvo C F , Bernard A , Huet S , Leroy E , Boumsell L , Senik A 
Published: December 2022

Abstract
In our previous paper, we demonstrated that anti-D44 MAb can, in the presence of complement, eliminate all the allocytotoxicity generated during a mixed lymphocyte reaction without affecting the alloproliferative response. As approximately 70% of CD4+ cells and 30% of CD8+ will be stained with anti-D44 MAb, we researched the functional role of the D44+ and D44- cells in each of these T cell subsets in the PWM-induced antibody response. We found that most of the helper activity for immunoglobulin (Ig) synthesis was mediated by CD4+ D44+ lymphocytes and that virtually all the suppressive activity was mediated by CD8+ D44- lymphocytes. Surprisingly enough, we noticed that the low level of Ig synthesis induced in B cells by CD4+ D44- lymphocytes could be strongly amplified by the addition of radiosensitive CD8+ lymphocytes, suggesting coexisting opposite immunoregulatory functions within the CD8+ T cell subset. These results, together with previous data, indicate that anti-D44 MAb subdivides T cells into subpopulations with distinct functional repertoires: a CD4+ D44+ helper subpopulation, a CD8+ D44+ cytotoxic subpopulation, and a CD8+ D44- suppressor subpopulation.
Down regulation of IL 2 mRNA by antibody to the 50-kd protein associated with E receptors on human T lymphocyte.
Authors: Tadmori W , Kant J A , Kamoun M 
Published: December 2022

Abstract
Recent studies have shown that antibodies to certain epitopes on the 50-kd molecule associated with sheep erythrocyte receptors on human T cells can suppress T cell proliferation and interleukin 2 (IL 2) elaboration. We used a human IL 2 cDNA clone to investigate the effect of antibody 9.6 and cyclosporin A (CsA) on the regulation of IL 2 mRNA levels in the cloned human leukemic T cell line Jurkat, J32. Maximal levels of IL 2 mRNA were reached 6 hr after induction of Jurkat cells with a combination of mitogen phytohemagglutinin (PHA) and phorbol ester (TPA). Antibody 9.6, added during the first 4 hr after lymphocyte stimulation, markedly inhibited IL 2 mRNA accumulation induced by low but synergistic combination of PHA (5 micrograms/ml) and TPA (1.0 ng/ml). The inhibition by 9.6 was not demonstrable as the concentration of PHA or TPA was increased. In contrast, the ability of CsA to suppress IL 2 mRNA accumulation appeared to be independent of PHA or TPA concentration and was minimal if CsA was added 4 hr after stimulation. IL 2 mRNA could be superinduced several folds by addition of cycloheximide 3 hr after induction of J32 with mitogens. Antibody 9.6 did not prevent IL 2 mRNA superinduction induced by cycloheximide, whereas CsA, as well as transcription inhibitor DRB, completely blocked this phenomenon. These findings indicate that signals induced by antibody 9.6 regulate IL 2 production at a pre-translational level, are operative for an extended period of time overlapping with the early phase of IL 2 mRNA accumulation, suppress IL 2 gene expression induced by PHA as well as TPA, and that antibody 9.6 and CsA exert their inhibitory effect by distinct mechanism(s).
A monoclonal antibody to the desmosomal glycoprotein desmoglein I binds the same polypeptide as human autoantibodies in pemphigus foliaceus.
Authors: Stanley J R , Koulu L , Klaus-Kovtun V , Steinberg M S 
Published: December 2022

Abstract
Recent studies have demonstrated that antibodies from about half of patients with pemphigus foliaceus (PF) bind to a 160 kd polypeptide ("PF antigen") in sodium dodecyl sulfate (SDS) extracts of normal human epidermis. Desmoglein (DG) I, a glycoprotein enriched in desmosomal cores, is approximately the same m.w. as PF antigen. To demonstrate that PF autoantibodies bind to DG I, we used a monoclonal IgG antibody (MmDGI-1) that was raised against bovine muzzle desmosomal cores, and that specifically binds DG I. Double immunofluorescence labeling was performed on the same section of normal human skin with PF antibodies, detected by fluorescein-conjugated goat anti-human IgG, and MmDGI-1, detected by rhodamine-conjugated goat anti-mouse IgG. The pattern of reactivity with both antibodies was identical. Immunoblotting studies on proteins extracted from normal human epidermis and separated by SDS-polyacrylamide gel electrophoresis demonstrated that PF antibodies and MmDGI-1 bound co-migrating polypeptide bands of approximate m.w. 160,000. To confirm that these were identical polypeptides, we performed immunoblots of these epidermal extracts that were separated by two-dimensional gel electrophoreses (isoelectric focusing followed by SDS-PAGE). PF antibodies and MmDGI-1 bound identical spots with pI approximately 5.4 to 5.7 and m.w. approximately 160,000. These studies demonstrate that autoantibodies from certain patients with PF, a disorder of cell adhesion, bind to DG I, a desmosomal core glycoprotein.
Immunologic and molecular characterizations of T cell-derived T cell activating factor.
Authors: Okada M , Yoshimura N , Ichimori Y , Kishimoto S , Nakai S , Nishino N , Kishimoto T 
Published: December 2022

Abstract
Culture supernatants from several subclones of a human T hybrid line (24A) stimulated with PMA showed co-stimulatory activity in the proliferation of Con A-stimulated murine thymocytes, but did not show any IL 2 activity. Some subclones did not show co-stimulatory activity even when stimulated with PMA, excluding the possibility of a carry-over effect. The factor found in the culture supernatants increased IL 2 production in normal T cells stimulated with a suboptimal concentration of PHA. The factor also induced IL 2 production in a T hybrid clone, T-394.1, when the latter was stimulated with a suboptimal concentration of mitogens, indicating a direct effect by this T cell-derived factor on mitogen-stimulated T cells inducing IL 2 production. This factor also induced the generation of other lymphokines such as BCDF and IFN-gamma. Northern blot analysis showed that the factor induced an increase in mRNA for IL 2 as well as IL 2 receptor. These results indicated that T cells could secrete a factor with IL 1-like activity. However, Northern blot analysis showed that mRNA from a T hybrid clone does not cross-react with cDNA for IL 1 (beta) derived from human monocytes.
A lymphokine distinct from interferon-gamma that activates human monocytes to kill Leishmania donovani in vitro.
Authors: Hoover D L , Finbloom D S , Crawford R M , Nacy C A , Gilbreath M , Meltzer M S 
Published: December 2022

Abstract
Human interferon-gamma (IFN-gamma), a T cell lymphokine (LK), activates monocytes to kill many intra- and extracellular pathogens. In fact, previous reports assert that all activity in LK for macrophage activation is due to IFN-gamma. To test this assertion, we examined monocyte interactions with amastigotes of Leishmania donovani after treatment with recombinant DNA or affinity-purified leukocyte IFN-gamma and IFN-gamma containing LK. Cells treated with at least 200 IU/ml IFN-gamma were microbicidal for L. donovani. Analysis of IFN-gamma dose responses for induction of microbicidal activity by recombinant IFN-gamma (r-IFN-gamma) and LK, however, documented a striking difference: LK was 25-fold more efficient than r-IFN-gamma at equivalent IFN-gamma titers. This large difference suggested that monocyte activation factor(s) in LK may not be IFN-gamma. Rabbit anti-IFN-gamma completely inhibited antiviral activity in LK but did not abrogate the ability to induce monocyte cytotoxicity against leishmania. Furthermore, removal of IFN-gamma from LK by monoclonal anti-IFN-gamma affinity chromatography or by treatment with anti-IFN-gamma followed by staphylococcal protein A chromatography also did not inhibit LK activity. Fractionation of LK on Sephadex G-100 revealed two activity peaks: one in the 50,000 to 60,000 m.w. range coincident with IFN-gamma, and the other at 25,000 to 30,000 daltons with no IFN-gamma. These studies document LK physicochemically and antigenically distinct from IFN-gamma that activate monocytes to kill L. donovani. Such novel factors may have broad import for the study of macrophage-mediated host defenses and for development of immunotherapeutic regimens.
Mechanisms of immunity to rickettsial infection: characterization of a cytotoxic effector cell.
Authors: Rollwagen F M , Dasch G A , Jerrells T R 
Published: December 2022

Abstract
Rickettsiae, as other intracellular bacteria, are relatively sequestered from the effects of antibody and local antibody-independent responses. Considering the obligate intracellular nature of rickettsia, the exact mechanisms by which lymphocytes and macrophages encounter rickettsial antigens and eliminate the infection depends upon the appropriate presentation of antigen to the immune system. We demonstrate here that cells taken from the spleens of Rickettsia typhi- or R. tsutsugamushi-infected mice are able to lyse specifically tissue culture targets infected with the homologous organism. This effect was eliminated upon treatment of the spleen cells with anti-Thy-1.2 + complement. Furthermore such T cells exhibit H-2-restricted killing when tested on infected targets of different genetic backgrounds. We propose that a T cell-mediated cytotoxic immune mechanism exists that may play an important role in the elimination of rickettsial organisms during infection.
A monoclonal antibody against LAV gag precursor: use for viral protein analysis and antigenic expression in infected cells.
Authors: Chassagne J , Verrelle P , Dionet C , Clavel F , Barre-Sinoussi F , Chermann J C , Montagnier L , Gluckman J C , Klatzmann D 
Published: December 2022

Abstract
A murine monoclonal antibody (MAb), named C.V.K., was produced after immunization with highly purified and sonicated lymphadenopathy-associated virus (LAV). No monoclonal antibody was observed with intact virus used as immunogen. C.V.K. MAb recognizes an epitope present on the precursor gag protein of 55 kilodaltons. Western blot analysis and pulse-chase experiments support the interpretation that after p55 cleavage into p25, p18, and p13, only p18 expresses this epitope. C.V.K. MAb selectively stained only LAV-infected lymphocytes. This intracytoplasmic staining appears 3 days after the infection and is correlated with reverse transcriptase activity. Neither membrane immunofluorescence of infected lymphocytes nor neutralizing activity was observed with C.V.K. MAb. These facts suggest that p55 and p18 are not expressed at the cell membrane or on the viral envelope. C.V.K. MAb should prove useful not only in the purification of core proteins but also for detecting infected cells producing the virus in suspension or on histologic sections.
Serologic and T cell recognition of truncated transplantation antigens encoded by in vitro deleted class I major histocompatibility genes.
Authors: McCluskey J , Bluestone J A , Coligan J E , Maloy W L , Margulies D H 
Published: December 2022

Abstract
Gene constructions encoding a leader sequence and the C2, transmembrane, and intracytoplasmic exons of both H-2Ld (pLd-C2) and H-2Dd (pDd-C2) were expressed as cell surface proteins when stably introduced into mouse L cells. Distinct proteins of 17.5 and 16 kd precipitated from pDd-C2 transformants reacted with a C2 domain-specific monoclonal antibody, whereas the pLd-C2 transformants expressed a single 19 kd glycoprotein. A xenoantiserum specific for the exon VI/VIII fusion peptide of H-2Dd precipitated only the 16 kd product, suggesting that this protein was derived from an alternately spliced transcript lacking exon VII of the native gene. CTL specifically recognized the pLd-C2 and pDd-C2 gene products, indicating the existence of CTL reactive against polymorphic determinants in the C2 domain of class I antigens.
Quantification of the strength of cell-cell adhesion: the capture of tumor cells by activated murine macrophages proceeds through two distinct stages.
Authors: Somers S D , Whisnant C C , Adams D O 
Published: December 2022

Abstract
The binding of tumor cells by macrophages activated with Bacillus Calmette-Guerin is a necessary step toward destruction of those cells. Although several characteristics of the interaction have been defined, little is known of how the actual binding process develops. We used a technique to quantify the forces required to disrupt cell-cell interactions. Over a range of applied relative centrifugal forces, the majority of targets that bound to the activated macrophages fell on two distinct plateaus. Approximately 90% of added targets were bound to the monolayers of macrophages over the range of 1 to 100 X G; 25 to 30% remained bound from 1200 X G to 1500 X G. Two strengths of binding, termed weak and strong binding, respectively, were thus defined on the basis of these curves. Strong binding developed only between activated macrophages and tumor cells. By contrast, weak interactions occurred between either activated or nonactivated macrophages and neoplastic or non-neoplastic target cells. The strong binding required time (60 to 90 min), metabolic activity by the macrophages, and trypsin-sensitive surface structures on the macrophages for development, whereas the weak interaction occurred rapidly and required none of these. Additional evidence indicated the weak binding developed into strong when activated macrophages bound neoplastic cells. This stabilization increased the strength of force to separate tumor cells from the macrophages at least approximately 15 fold (i.e., from approximately 16 mu dynes/cell to approximately 240 mu dynes/cell). Of note, the development of strong binding of antibody-coated targets had distinct requirements for establishment. Taken together, the data suggest the stabilization of binding (i.e., the development of weak into strong binding) leading to effective cell-cell interaction is a complex and dynamic process that may vary depending upon the recognition system involved.
Immunochemical characterization of two antigens recognized by new monoclonal antibodies against human colon carcinoma.
Authors: Girardet C , Vacca A , Schmidt-Kessen A , Schreyer M , Carrel S , Mach J P 
Published: December 2022

Abstract
Two different monoclonal antibodies (MAb), called L-D1 and L-C5, were produced after immunization with either intact cells or the methanol phase of glycolipid extracts, respectively, from the same human colon carcinoma line, LoVo. As determined by an antibody-binding radioimmunoassay (RIA) on intact cells, MAb L-D1 and MAb L-C5 were highly reactive with all five colon carcinoma lines tested and with only one out of the 21 cell lines of various tissue origin tested. No reactivity of either MAb was observed with peripheral blood lymphocytes, granulocytes, or erythrocytes from healthy donors of various blood groups. Both MAb were tested in competitive binding experiments with an anti-CEA MAb from our laboratory (CEA 35) and with two previously described anti-colon carcinoma MAb from the Wistar Institute called 1083-17-1A (17-1A) and NS-19.9. In competitive binding experiments, MAb L-D1 was inhibited by MAb 17-1A and reciprocally, whereas MAb L-C5 was not inhibited by any of the other MAb tested. MAb L-D1 precipitated a major protein band with an apparent molecular weight (MW) of 41 kilodaltons (kD); interestingly, MAb 17-1A, which was reported to react with an uncharacterized antigen, precipitated the same protein band of 41 kD. This was confirmed with immunodepletion experiments. Furthermore, after treatment of the colon carcinoma cell line with tunicamycin, both MAb L-D1 and 17-1A precipitated a protein band of 35 kD. This shift of 6 kD suggests that the glycoprotein recognized by these 2 MAb contains two to three N-linked carbohydrate side chains. MAb L-C5 precipitated a group of three to four protein bands ranging from 43 to 53 kD that were not modified by tunicamycin treatment. A preliminary study conducted by using immunoperoxidase labeling on frozen sections of primary colon carcinoma showed that the two new MAb react strongly with these tumors, but also weakly with the normal adjacent mucosa, as did the other anti-colon carcinoma MAb tested.
Isotype-like suppression of T cell-mediated immunity in vivo. I. Delayed-type hypersensitivity specificity of T cell suppression induced by antigen-binding T cell factors that initiate contact sensitivity.
Authors: Ptak W , Bereta M , Ptak M , Askenase P W 
Published: December 2022

Abstract
A new form of immunoregulation is described that is based on the recent suggestion that the effector phase of delayed-type hypersensitivity (DTH) responses consists of a cascade of steps that are dependent on the sequential action of two types of antigen-specific Ly-1+ effector cells. According to this formulation, which is based on analysis of contact sensitivity (CS) in mice, DTH consists of at least two T cell-dependent steps that must occur in sequence. The first of these steps occurs within 2 hr of challenge and depends on DTH-initiating, antigen-binding, antigen-specific T cell factors that sensitize the tissues for an obligatory initial vasoactive step, which allows the antigen/major histocompatibility complex (MHC)-restricted, Ly-1+ effector T cells of classic 24 to 48 hr DTH responses to enter the tissues and produce chemoattractant lymphokines. We have now found that nonspecific suppression of CS responses can be induced by i.v. injection of these antigen-binding, CS-initiating T cell factors. Injection of the antigen-binding T cell factor induces Ly-2+, I-J-, cyclophosphamide sensitive, seemingly nonspecific suppressor T cells to inhibit initiation of CS responses. These suppressor cells do not affect the late-acting lymphokine-producing T cells, but probably act by preventing production of antigen-specific factors of the type that are required to initiate DTH responses. Furthermore, injection of CS-initiating antigen-binding T cell factors also induces suppression of sheep red blood cell (SRBC)-specific DTH, but does not affect classic anti-SRBC B cell responses, which are dependent on antigen/MHC-restricted Ly-1+ helper T cells; skin allograft rejection responses are also not affected. Thus, the suppression is DTH-specific. In addition, suppression induced by antigen-binding T cell factors is Igh and not MHC/H-2 restricted. These findings and data in the companion manuscript showing that these suppressor T cells act by production of soluble suppressor factors that bind to antigen-specific T cell factors of different antigenic specificities, cause us to suggest that the antigen-binding T cell factors are T cell isotype-like. Therefore, an isotype-like suppression is induced by these factors. This isotype-like suppression affects factor-producing cells of various antigenic specificities, may be mediated by T cell isotype-binding factors that are Igh restricted and block initiation of DTH responses, but does not affect conventional, antigen/MHC-restricted T cells, which may therefore have antigen receptors of a different isotype.