bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of type III pneumococcal polysaccharide-specific suppressor T cells in cyclophosphamide-treated mice requirement for recognition of antigen and I-J determinants on antigen coupled to syngeneic spleen cells.
Authors: Braley-Mullen H 
Published: December 2022

Abstract
Type III pneumococcal polysaccharide (S3) coupled to spleen cells (S3-SC) is a potent tolerogen in mice. Although tolerance induced by S3-SC has been shown to be T cell dependent, T cells from tolerant mice are unable to actively suppress the antibody response to S3 when transferred to normal mice. However, when mice are given cyclophosphamide (Cy) before injection of S3-SC, suppressor T cells (Ts) are induced and can be detected by their ability to suppress the response to S3 after transfer to normal mice. The Ts induced by S3-SC in Cy-treated mice are antigen specific and can bind to and be eluted from plates coated with a soluble membrane preparation of S3-SC (S3-SCSM) prepared from mice that are syngeneic with mice in which Ts are induced. Allogeneic S3-SCSM, free S3, or S3 coupled to non-membrane carriers do not bind the Ts. Moreover, under the same conditions, detectable Ts were not induced by free S3 in either normal or Cy-treated mice. These results suggest that these Ts are activated by, and have receptors for, S3 plus a self cell membrane determinant. The self cell membrane determinant required for Ts induction is apparently I-J since Ts are induced only when the antigen-coupled spleen cells share I-J with the Cy-treated mice in which Ts are activated. The necessity to treat mice with Cy to obtain detectable Ts is presumably due to the fact that S3-SC activates a contrasuppressor T cell in normal mice which interferes with Ts function, and this cell is eliminated by Cy.
Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester.
Authors: Thiele D L , Kurosaka M , Lipsky P E 
Published: December 2022

Abstract
The lysosomotropic compound L-leucine methyl ester (Leu-OMe) was utilized to delineate the phenotype of the accessory cells involved in human B and T cell activation in vitro. Leu-OMe was shown to cause lysosomal disruption and selective death of human monocytes (M phi). After 30-45 minute incubations with this agent, human peripheral blood mononuclear cells (PBM) were nearly completely depleted of M phi. Associated with this M phi depletion, PBM were rendered unresponsive to a variety of T and B cell mitogens including the plant lectins phytohemagglutinin, concanavalin A, and pokeweed mitogen as well as the oxidative mitogens sodium periodate and neuraminidase plus galactose oxidase. Leu-OMe mediated loss of responsiveness was the result of a selective loss of an accessory cell necessary for each of these responses since reconstitution was accomplished by the addition of a M phi-enriched adherent cell population. While intact adherent cells could reconstitute responsiveness, crude M phi supernatants or highly purified human IL 1 alone were ineffective. Further identification of the Leu-OMe sensitive accessory cell indicated that it was entirely contained within the fraction of the adherent population identified by the monoclonal anti-M phi antibody, 63D3. The mechanism by which Leu-OMe Killed M phi was dependent on the lysosomal content of these cells, since agents that altered lysosomal enzyme activity such as chloroquine or NH4Cl protected M phi from Leu-OMe. Thus, the selective killing of M phi by Leu-OMe appeared to relate to the characteristically rich endowment of lysosomes within these cells. These results support the conclusion that a lysosome-rich, leucine methyl ester-sensitive, intact M phi identified by the monoclonal anti-M phi antibody 63D3 is the circulating accessory cell required for mitogen-triggered human B and T cell activation.
Permissive role of calcium in the inhibition of T cell mitogenesis by calmodulin antagonists.
Authors: Cheung R K , Grinstein S , Gelfand E W 
Published: December 2022

Abstract
The importance of Ca++ in the initiation of lymphocyte activation and mitogenesis has been supported by several studies. Because calmodulin functions as the intracellular mediator of the effects of Ca++, it likely plays a major role in the regulation of lymphocyte function. We have examined the effects of known calmodulin antagonists, the phenothiazines, on lectin-induced T cell mitogenesis and have shown a central role for Ca++ uptake in the expression of a phenothiazine-sensitive stage after lectin activation. The drug effects were observed only if the cells were previously activated by PHA or the ionophore A23187, and only in the presence of Ca++. These effects were restricted to a defined time period (5 hr) after lectin activation. The data support the concept that calmodulin is the target for the phenothiazine effects and demonstrate the permissive role of Ca++ in the mediation of these events.
Alloantigen-specific cytotoxic and suppressor T lymphocytes are derived from phenotypically distinct precursors.
Authors: Damle N K , Mohagheghpour N , Hansen J A , Engleman E G 
Published: December 2022

Abstract
Although Leu-2+ (OKT8+) T cells activated in the mixed lymphocyte reaction (MLR) mediate both alloantigen-specific cytotoxicity and suppression of alloantigen-induced proliferation, it is not known whether these functions derive from a single cell type or phenotypically distinct cells. This study was undertaken to examine the alloantigen-specific cytolytic and suppressor potential of two subpopulations of Leu-2+ cells distinguishable from one another on the basis of their binding to the monoclonal antibody 9.3. Leu-2+, 9.3+ and Leu-2+, 9.3- populations were purified from peripheral blood, cultured for 7 days with autologous helper/inducer (Leu-3+) cells and allogeneic non-T cells, and reisolated before testing for cytotoxicity and suppression. All detectable alloantigen-specific cytolytic activity was confined to the Leu-2+, 9.3+ subpopulation. Killing by this subset was specific for the HLA-A and B (class I) major histocompatibility complex (MHC) antigens of the priming cell. By contrast, suppression of proliferation was mediated predominantly by the Leu-2+, 9.3- cells, and suppression by this subpopulation was specific for the HLA-DR (class II) MHC antigens of the priming cell. The development of suppression by Leu-2+, 9.3- cells was unaffected by cyclosporin A (CsA), an agent shown previously to block the development of cytolytic but not suppressor cells in MLR. Alloactivated Leu-2+, 9.3+ cells were slightly inhibitory of fresh MLR, but this effect as well as the development of cytolytic cells was completely abrogated by CsA. These results indicate that suppressor and cytolytic Leu-2+ T cells activated in MLR are derived from distinct precursors separable by antibody 9.3.
T lymphocyte line specific for thyroglobulin produces or vaccinates against autoimmune thyroiditis in mice.
Authors: Maron R , Zerubavel R , Friedman A , Cohen I R 
Published: December 2022

Abstract
We investigated Ly-1+ T lymphocyte line cells specifically reactive to thyroglobulin (Tg) that were isolated from mice primed with mouse Tg in adjuvant. Intravenous inoculation of as few as 10(5) line cells was sufficient to cause severe and prolonged thyroiditis in recipient mice that were intact, irradiated, or athymic nudes. Disease was independent of circulating Tg antibodies, suggesting that anti-Tg T lymphocytes could cause thyroiditis unaided by antibodies. Thyroiditogenic T lymphocytes could be isolated as cell lines from apparently healthy mice that had been immunized with non-thyroiditogenic bovine Tg in adjuvant, which indicates that autoimmune effector T lymphocytes may develop covertly in the course of immunization with foreign antigens. Finally, a single i.v. inoculation of anti-Tg T lymphocyte line cells attenuated by irradiation vaccinated mice completely against subsequent development of autoimmune thyroiditis produced either by active immunization to Tg or by passive transfer of intact line cells. Vaccinated mice that were protected from inflammatory lesions of thyroiditis still produced high titers of Tg antibodies in response to active immunization. Thus, vaccination specifically inhibited thyroiditogenic T lymphocytes but not helper T lymphocytes required for the production of Tg autoantibodies.
Characterization of human K cells by surface antigens and morphology at the single cell level.
Authors: Wåhlin B , Perlmann P 
Published: December 2022

Abstract
Human lymphocytes killing bovine erythrocytes in vitro in antibody-mediated reactions were characterized at the effector cell level in the ADCC plaque assay. Five to 10% of highly purified peripheral blood lymphocytes are active K cells in this system. Forty to 50% of these were T gamma cells expressing the T cell-associated surface antigens T3 and Leu-1. These cells also expressed the T8/Leu-2a antigens (approximately 20%) or the T4/Leu-3a antigens. Although approximately 30% of the K cells were T4+ when examined after completion of the ADCC assay (18 hr), only less than 10% were T4+ (and Leu-3a+) when examined before the assay. The results indicated that exposure to antigen/antibody complexes during the assay induced increased T4 expression, probably linked to Fc gamma R modulation on some initially T4-/T3+ lymphocytes. The expression of the other antigens (including Leu-3a) was not affected by exposure of the lymphocytes to antigen/antibody complexes. Two-color fluorescence experiments further demonstrated that a minor fraction (10 to 20%) of the K cells carrying T cell-associated antigens also expressed the monocyte/null cell-associated antigen M1 as detected with the monoclonal antibody OKM1. A second major category of effector cells, composed of at least 25% of the K cells, were large granular lymphocytes (LGL) that lacked detectable T cell-associated antigens but expressed the HNK-1 (Leu-7) as well as the M1 antigen. As seen from the size of the plaques formed by different effector cells, K cells of the LGL type had a greater recycling capacity and/or cytolytic efficiency than those of T gamma type.
Mechanism of macrophage-mediated cytotoxicity: production of a soluble cytotoxic factor.
Authors: Drysdale B E , Zacharchuk C M , Shin H S 
Published: December 2022

Abstract
Peritoneal macrophages from C3HeB/FeJ mice became cytotoxic for 6C3HED lymphosarcoma cells, P815 mastocytoma cells, and L-929 fibroblasts when treated with the calcium ionophore, A23187, at concentrations ranging from 1.0 to 20 microM. The effect of A23187 on other activation processes was also tested. It was found that A23187 and lipopolysaccharide (LPS) acted synergistically, but no consistent synergy with macrophage-activating factor (MAF) was observed. Cytotoxic activity (M phi-CF) was found in cellfree supernatants from M phi activated by A23187 or LPS. Furthermore, these two activating agents synergize in the production of M phi-CF. The cytotoxic activity of the crude material was not blocked by catalase or protease inhibitors. Fractionation of supernatants by high pressure liquid chromatography has shown that there was a peak of cytotoxic activity with a m.w. of approximately 45,000. Interestingly, L-929 cells were 30-fold more sensitive to M phi-CF than a lymphotoxin-resistant subline of L-929.
Lymphokines secreted by an established lymphocyte line modulate receptor-mediated endocytosis in macrophages derived from human monocytes.
Authors: Fogelman A M , Seager J , Groopman J E , Berliner J A , Haberland M E , Edwards P A , Golde D W 
Published: December 2022

Abstract
As little as 1 microliter of serum-free supernatant from Mo(t), an established lymphocyte line, when added to a 500-microliters incubation of macrophages derived from human monocytes, significantly decreased the receptor-mediated uptake and degradation of three cholesterol-rich molecules: low density lipoprotein (LDL); LDL complexed to dextran sulfate; and LDL modified by malondialdehyde (MDA-LDL). In contrast, the receptor-mediated uptake and degradation of mannosyl bovine serum albumin was increased three-fold. The Mo(t) supernatant did not contain competitive inhibitors of the cholesterol-rich ligands, and it did not alter macrophage receptor-independent endocytosis, protein synthesis, or phagocytosis of heat-killed yeast. The effect of the Mo(t) supernatant was specific for macrophages and was abolished by preincubation of the supernatant with trypsin, which indicates that the active substances are protein in nature. The decrease in the uptake and degradation of MDA-LDL induced by preincubating the macrophages with Mo(t) supernatant appeared to result from a decrease in the number of receptors for this ligand at the cell surface. The isolation of these lymphokines should offer new insights into macrophage receptor-mediated endocytosis, and may yield substances useful in preventing foam cell formation in atherosclerosis.
Enhanced responsiveness of committed macrophage precursors to macrophage-type colony-stimulating factor (CSF-1) induced in vitro by interferons alpha + beta 1.
Authors: Moore R N , Rouse B T 
Published: December 2022

Abstract
Contrasting effects of interferon alpha + beta (IFN) on colony-stimulating factor- (CSF) induced macrophage stem cell proliferation resulted when nucleated murine femoral marrow cells were exposed to IFN either before addition of CSF or simultaneously with CSF. Responsiveness to macrophage type L cell CSF was measured by two different assays: by determination of [3H]thymidine (3H-TdR) incorporation and by enumeration of colonies formed in response to CSF. Incubation of nucleated marrow cells concurrently with CSF and IFN resulted in depressed proliferation that was dependent on the dose of IFN. Preincubation of marrow cells with IFN, however, produced a dose-dependent enhancement of CSF responsiveness in comparison to preincubation of marrow cells in the absence of IFN. The enhancing effect of IFN was observed only when preincubated cells were stimulated with suboptimal concentrations of CSF. At optimal CSF concentrations, differences were not observed in either 3H-TdR incorporation or in colony formation. On the basis of data accumulated by both assays for CSF responsiveness, IFN pretreatment was hypothesized not to increase the total population of existing progenitor cells, but to influence the capacity of pre-existing progenitor cells to respond to suboptimal doses of the growth factor.
Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule.
Authors: Dialynas D P , Quan Z S , Wall K A , Pierres A , Quintáns J , Loken M R , Pierres M , Fitch F W 
Published: December 2022

Abstract
Monoclonal antibody GK1.5 recognizes a previously undescribed murine T cell surface molecule, designated L3T4, which migrates on SDS-PAGE under reducing conditions as a single band with an apparent m.w. of 52,000. L3T4 is expressed by approximately 80% of thymocytes and by approximately 20% of spleen cells. There appears to be poor correlation between expression of L3T4 by functional T cell clones and expression of Lyt-2, expression of the cytolytic phenotype, and class I MHC antigen reactivity. On the other hand, both a class II MHC antigen-reactive HTL clone and an Lyt-1- Mls-reactive HTL clone express L3T4. Analysis of the effect of mAb GK1.5 on PFC responses in adoptive transfer suggests that L3T4 is expressed by the helper/inducer subset of murine T cells. Expression of L3T4 by murine T cells, however, may correlate primarily with class II MHC antigen reactivity rather than with functional phenotype; mAb GK1.5 profoundly blocks antigen-specific cytolysis by the cloned class II MHC antigen-reactive CTL line A15-1.17. Antigen-specific cytolysis by A15-1.17 is blocked by mAb GK1.5 at a step before the lethal hit. Collectively, the flow cytometric, functional, and biochemical data indicate that L3T4 is similar to the human Leu-3/T4 molecule.
A unique DR-related B cell differentiation antigen.
Authors: Shipp M A , Schwartz B D , Kannapell C C , Griffith R C , Scott M G , Ahmed P , Davie J M , Nahm M H 
Published: December 2022

Abstract
The Ia or class II molecules in both mouse and man are the basis for the genetic control of the immune response. In addition to DR, other class II antigens have been described in man. We describe a new human Ia antigen K19, recognized by three monoclonal antibodies (HK-9, HK-19, and HK-20). This antigen has the general biochemical characteristics of an Ia antigen but is different from a DR antigen. Further, this antigen is found only on mature B lymphocytes and not on monocytes and activated T cells. Thus, this antigen may represent a new Ia-like molecule that is preferentially expressed on mature B cells.
The asymmetry in idiotype-isotype expression in the response to phosphocholine is due to divergence in the expressed repertoires of Lyb-5+ and Lyb-5- B cells.
Authors: Wicker L S , Guelde G , Scher I , Kenny J J 
Published: December 2022

Abstract
The X-linked CBA/N immune defect was used to investigate the roles of Lyb-5- and Lyb-5+ B cells in the memory response to PC-KLH (phosphocholine-conjugated keyhole limpet hemocyanin). (CBA/N X BALB/c)F1 (CB) male mice express the xid mutation and thereby lack the Lyb-5+ B cell subset, whereas their female littermates are normal and express both Lyb-5+ and Lyb-5- B cells. After priming with PC-conjugated hemocyanin (PC-Hy) in complete Freund's adjuvant, female B cells produce three phenotypic sets of PC-KLH-specific antibody. The first set (group I) is dominated by T15+, IgM, IgA, and IgG3, PC-specific antibodies. The second subset (group II) is specific for phenylphosphocholine (PPC), and is dominated by T15-, IgG1, and IgG2 antibodies. The third set (group III) recognizes an epitope(s) composed of both the PPC hapten and carrier determinants. PC-Hy-primed B cells from immune defective CB male mice produce the same number of IgG1 and IgG2 plaque-forming cells (PFC) as do PC-Hy-primed normal female cells, and these PFC are also predominantly T15- and PPC specific (group II). In addition, a significant amount of group III IgG1 and IgG2 antibody is observed in the immune defective male response. In contrast to female B cells, immune defective male B cells produce a low IgM, IgA, and IgG3 memory response that is not composed of PC-specific (group I) antibodies; in fact, most of these antibodies arise from group III precursors and are not inhibited by either PC or PPC. PC-specific antibodies usually represent less than 25% of the anti-PC-KLH response in immune defective mice; however, these PC-specific antibodies are predominantly T15-. These data suggest that the Lyb-5-B cells in both normal and immune defective mice produce the T15-, IgG1, and IgG2 antibodies that dominate the secondary immune response to PC-KLH, and that the Lyb-5+ B cells produce the T15+, IgM, IgA, and IgG3 portion of the secondary response in normal mice. This hypothesis was confirmed by priming normal mice with the R36a strain of Streptococcus pneumoniae or with PC-Hy in saline. These forms of PC-antigen prime only the Lyb-5+ B cell subset. The adoptive transfer of these two B cell sources results in an anti-PC-KLH response that is T15 dominant and totally PC inhibitable.(ABSTRACT TRUNCATED AT 400 WORDS)
Monoclonal antibodies against T cell differentiation antigens initiate stimulation of monocyte/macrophage oxidative metabolism.
Authors: Descamps-Latscha B , Golub R M , Nguyen A T , Feuillet-Fieux M N 
Published: December 2022

Abstract
Within the first minute after incubation with the mouse anti-human T cell orthoclone monoclonal antibodies OKT3, OKT4, and OKT8, and in the absence of complement, human monocytes generate a burst of highly reactive oxygen metabolites as detected by a luminol-dependent photometric chemiluminescence (CL) assay. The kinetics of the CL responses to these antibodies are identical to that induced by OKM1, the monoclonal antibody to human monocytes and granulocytes. With regard to CL response intensities, OKM1 induces the maximal response and those of OKT3, OKT4, and OKT8 closely reflect the proportion of T cell subsets recognized by these antibodies in peripheral blood. This reaction is also observed when monoclonal antibodies against mouse Lyt surface determinants (Lyt-1 and Lyt-2) and Thy-1 antigen are tested against murine spleen cells. This murine model was further used to investigate the specificity and the mechanism of this reaction. It was demonstrated that the CL response is Lyt antigen specific, occurs upon addition of monoclonal IgG but not IgM antibodies, requires the concomitant presence of CL-producing cells (CLPC) (promonocytes, monocytes, macrophages, and/or granulocytes) and of fully differentiated T cells, and lastly, is mediated via a T cell opsonization process. Selective blockade of bone marrow cell Fc receptors (FcR II) with monoclonal anti-mouse FcR II antibody inhibits the CL response to IgG2b anti-T cell antibody-coated thymocytes and thus strongly suggests that the stimulation of CLPC oxidative metabolism in this model results from the binding of opsonized T cells to plasma membrane Fc receptors. These observations lend additional support to increasing evidence that the initiation of effector functions by monoclonal anti-T cell antibodies may be strictly dependent upon the presence of monocytes and/or macrophages.
Nonspecific cytotoxicity of vaccinia-induced peritoneal exudates in hamsters is mediated by Thy-1.2 homologue-positive cells distinct from NK cells and macrophages.
Authors: Yang H , Tompkins W A 
Published: December 2022

Abstract
Vaccinia virus-induced peritoneal exudate cells (PEC) in the hamster were characterized with regard to cell type(s), target specificity, and expression of the T cell antigen, Thy 1.2 homologue. Hamsters were immunized intraperitoneally with vaccinia virus and cytotoxicity was measured against 51Cr-labeled targets in a 16-hr assay. PEC collected 4 days after immunization were cytotoxic for both baby hamster kidney cells (BHK) and herpes virus-infected BHK (BHKHSV). Both the nonadherent (lymphocyte) and adherent macrophage (MP) fractions of PEC were cytotoxic. Treatment of cells with a monoclonal anti-murine Thy 1.2 antibody (alpha-Thy 1.2) known to detect a Thy 1.2 homologue on hamster T cells, removed all of the cytotoxicity in both PEC fractions, whereas, cytotoxic spleen cells from the same animals were resistant to antibody treatment. Similarly, the cytotoxic cells in PEC induced by bacillus Calmette-Guérin were exclusively of the Thy 1.2 homologue-positive phenotype. Target specificities of Thy 1.2+ PEC and Thy 1.2- spleen cells were similar as evidenced by comparable activity against hamster BHK and BHKHSV targets and murine SV3T3 and YAC-1 targets. Previous studies have attributed the cytotoxicity of the adherent PEC to MP. However, as determined by immunofluorescence and morphological studies, treatments that enriched for MP decreased cytotoxic activity, whereas, procedures that enriched for lymphocytes enhanced cytotoxic activity suggesting that all cytotoxicity in PEC is mediated by a non-specific Thy 1.2 homologue positive lymphocyte (Thy 1.2+ CL). Thus our data support the conclusion that intraperitoneal inoculation of hamsters with vaccinia induces two distinctly compartmentalized phenotypes with similar cytotoxic characteristics--the Thy 1.2+ CL and the Thy 1.2 homologue-negative natural killer cell (NK) or NK-like cell in the peritoneum and in the spleen, respectively.