bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-mediated lympholytic responses against autologous cells modified with haptenic sulfhydryl reagents. V. H-2Ld self products are recognized by anti-AED-specific cytotoxic T cells.
Authors: Levy R B , Shearer G M 
Published: December 2022

Abstract
The present studies were designed to examine the restriction elements involved in the H-2d haplotype CTL response against AED-self. BALB/c mice were immunized by in vivo administration of syngeneic BALB/c spleen cells conjugated with the sulfhydryl reactive haptenic reagent I-AEDANS. The cytotoxic T cell response generated by subsequent in vitro stimulation with AED-self was found to contain H-2K and H-2D region-specific components. In contrast to the predominant H-2D hapten-self CTL responses induced by amino-reactive haptenic reagents like TNBS and FITC, the AED-self response was predominantly directed against H-2K self products. Antibody inhibition analysis demonstrated that the H-2D region component contained Ld-AED-self CTL, as well as Dd-AED-self CTL. However, although both Ld- and Dd-restricted components could be identified shortly (less than 1 wk) after priming, the H-2D region AED-self CTL response shifted to a single restricting molecule, namely Dd, 1 wk and later after immunization. The results of this study provide the first demonstration that the H-2L locus encodes a cell surface product that can function as a restricting molecule for hapten-self-specific CTL. The shift from Ld and Dd AED-specific CTL to Dd only suggests the existence of a highly specific regulatory mechanism directed against antigen (i.e., hapten) plus self.
The diversity of T cell receptors specific for self MHC gene products.
Authors: Siliciano R F , Brookmeyer R , Shin H S 
Published: December 2022

Abstract
Cytolytic and helper T cells exhibit, in addition to their specificity for foreign antigen, a restriction specificity for self MHC gene products. The present study was designed to assess the degree of diversity within the repertoire of receptors that are involved in T cell recognition of self MHC gene products. For this purpose, we generated a series of murine cytolytic T lymphocyte (CTL) clones specific for a hapten antigen and restricted to the self MHC gene product H-2Kb. An analysis of the hapten fine specificity of these clones by using hapten analogues revealed the presence of substantial diversity within the repertoire of CTL receptors specific for the hapten. The degree of diversity within the repertoire of self H-2 recognition structures on these clones was assessed by testing clones on panels of syngeneic, congenic H-2K disparate, and H-2Kb mutant target cells bearing varying amounts of antigen. A striking degree of heterogeneity in H-2K recognition was found among these H-2Kb restricted CTL. We estimate that there are probably a minimum of 65 different patterns of H-2K recognition among these clones. Our results suggest a high degree of diversity exists within the repertoire of self MHC recognition structures on antigen-specific T cells restricted to a single self MHC gene product.
MHC-linked Ir gene control of T cell responses: GAT-specific proliferating T cells and helper T cells are elicited in nonresponder mice immunized with soluble GAT.
Authors: Gougeon M L , Theze J 
Published: December 2022

Abstract
The immune response to the synthetic terpolymer GAT is controlled by MHC-linked Ir gene(s). We show in this paper that antigen-presenting cells and T cells from mice belonging to two nonresponder strains (SJL and DBA/1) can present and recognize GAT, respectively. This has been measured with a T cell proliferation assay of GAT-primed lymph node cells. In order to detect T cell proliferation among GAT-primed lymph node cells from DBA/1 mice, it is necessary to treat the cells with monoclonal anti-Lyt-2 antibodies and complement (C) before the assay. These conclusions were further verified with SJL mice, when a T cell line derived from LN cells was used. We have shown that after immunization with GAT, specific T helper cells can be generated in the lymph nodes of SJL mice but not in the lymph nodes of DBA/1 mice. Furthermore, GAT-specific T helper cells can be detected in the spleen of SJL mice after immunizations with GAT, provided these spleen cells are pretreated with monoclonal anti-Lyt-2 antibodies + C or mild irradiation. Together, these results support the general idea that nonresponsiveness can be explained by a regulatory imbalance rather than by discrete cellular "defects."
Acquisition of deoxyguanosine resistance by TPA-induced T lymphoid lines.
Authors: Sacchi N , Fiorini G , Plevani P , Badaracco G , Breviario D , Ginelli E 
Published: December 2022

Abstract
The human leukemic T cell line 8402, which contains terminal deoxynucleotidyl transferase (TdT) and phenotypically resembles precursor thymocytes, when exposed to the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) undergoes in vitro T maturation. TdT disappears from virtually all the cells and a fraction of TdT- -cells express specific T surface markers, such as the T3 determinant. Like T lymphocytes from the thymus, 8402 cells are extremely sensitive to the cytotoxic effect of deoxyguanosine (dGuo). As a consequence of TPA treatment, resistance to dGuo is observed in 8402, as well as in two other TdT+ lymphoid T cell lines, Molt-4 and CEM-10. These results suggest the occurrence of changes in deoxynucleoside metabolism in TPA-treated cells related to the in vitro maturation process. Maturation of 8402 cells, once started, progresses in the presence of additional physiologic stimuli provided by conditioned medium from lymphocyte culture, because a portion of cells display the T8+/T4- phenotype characteristic of cytotoxic/suppressor T cells. This in vitro lymphoid system may thus be used to study the relationships of molecular differentiation between precursor thymocytes and cytotoxic/suppressor T cells.
Heterogeneity of human NK cells: comparison of effectors that lyse HSV-1-infected fibroblasts and K562 erythroleukemia targets.
Authors: Fitzgerald P A , Evans R , Kirkpatrick D , Lopez C 
Published: December 2022

Abstract
In this study, we compared the natural killer (NK) cells that lyse HSV-1-infected NK(HSV-1) or uninfected [NK-(FS)] fibroblasts to those that lyse K562 erythroleukemia cells [NK(K562)]. Activity against all three targets was found in Percoll gradient fractions enriched for large granular lymphocytes, which suggests that these effector cells have a common morphology. In competition studies between 51Cr-labeled targets and unlabeled targets, both the infected and the uninfected fibroblasts competed for lysis of NK(HSV-1) and NK(FS) activity, whereas K562 cells competed poorly. In contrast, when 51Cr-labeled K562 cells were used, the unlabeled K562 cells competed well, but HSV-1-infected and uninfected fibroblasts competed poorly. Panning studies and complement elimination experiments using monoclonal antibodies were performed to describe cell surface markers on the NK cell populations. Treatment with an antibody to an la framework antigen reduced NK(HSV-1) but not NK(K562) activity. In contrast, the majority of NK(K562) effectors were recognized by antibodies to the E-rosette receptor (Lyt-3 and OKT11A), whereas NK(HSV-1) activity was much less sensitive to this antibody. OKM1, OKT10, and Leu-7 (HNK-1) markers were found on a portion, but not all, of the cells that lysed both the HSV-FS and K562 targets, while treatment with HLA plus complement totally abrogated both NK activities. Taken together, these data are consistent with the concept that human NK cells are heterogeneous and that we are dealing with at least three subpopulations of effector cells--one that kills the infected or uninfected fibroblasts; one that kills K562 cells; and a third population that may be able to kill all three targets. Patient studies provide additional evidence for heterogeneity within the NK cells that lyse the fibroblasts and K562 cells. We have studied a number of individuals who have normal NK activity with one target (HSV-FS or K562) but have low or no activity against the other. These patients provide strong evidence not only that NK cells are heterogeneous but also that these NK subpopulations can be regulated independently of each other in vivo.
Expression of C3b receptors on human be cells and myelomonocytic cells but not natural killer cells.
Authors: Tedder T F , Fearon D T , Gartland G L , Cooper M D 
Published: December 2022

Abstract
We have examined natural killer (NK) cells, B cells and myelomonocytic cells at different stages of differentiation for the expression of surface C3b receptors (C3bR). Receptor presence was detected using affinity-purified F(ab')2 anti-C3bR antibodies in indirect immunofluorescence assays. NK cells, identified in fetal and adult tissues by the monoclonal antibody HNK-1, were C3bR- except for infrequent C3bR+ HNK-1+ cells in some blood samples. NK cells were not induced to express C3bR by exposure to interferon, target cells, or phorbol myristate acetate. B cells gradually acquired the ability to express C3bR with maturity: 15% of large pre-B cells were C3bR+, 35 to 48% of small pre-B, 60 to 80% of immature B, and 99% of mature B cells. Mature plasma cells were rarely C3bR+. Myelomonocytic cells acquire C3bR relatively late during their development, with neutrophils beginning to express C3bR during the band stage of differentiation. All adult blood myelomonocytic lineage cells, identified by the monoclonal antibody MMA and by morphology, were C3bR+.
Analysis of vascular lesions in murine SLE. I. Association with serologic abnormalities.
Authors: Berden J H , Hang L , McConahey P J , Dixon F J 
Published: December 2022

Abstract
In murine SLE, two different vascular lesions can develop. A necrotizing polyarteritis (NPA), exclusively found in MRL/I mice, is characterized by a dense infiltration of PMN and fibrinoid necrosis of the arterial wall. The second, a degenerative vascular lesion, occurs in a low incidence in all SLE mice, except the (NZW X BXSB)F1 (WBF1) male, in which its incidence is 100%. This lesion shows subendothelial deposits of immunoglobulins with minimal or no inflammatory or proliferative reaction. This degenerative vascular disease (DVD) is predominantly localized in the coronary arteries and is highly correlated with myocardial infarction. Serologic analysis revealed that NPA in MRL/I mice was associated with relatively late development of high levels of autoantibodies and circulating immune complexes; DVD in WBF1 mice was associated with an early onset of autoantibody production of a low magnitude that gave rise to a persistent low level of circulating immune complexes. Characterization of circulating immune complexes in MRL/I mice showed these complexes were mainly of intermediate size (7S-19S) and contained predominantly anti-DNA antibodies. In WBF1 mice, complexes were barely detectable and contained mostly anti-gp70 antibodies. Elution of kidneys showed that the major antibody deposited in MRL/I mice has an anti-DNA specificity, whereas in WBF1 animals, the major antibody was anti-gp70. Furthermore, a 10 times greater amount of immunoglobulins could be eluted from WBF1 hearts with DVD than from MRL/I and BXSB hearts. Additionally, we found that the lack of an inflammatory reaction in DVD was not because of a preferential deposition of noncomplement-fixing IgG1 antibodies nor could it be related to a defective inflammatory response, because WBF1 mice had an undiminished reverse passive Arthus reaction throughout their lives. It is concluded that NPA develops secondary to high levels of autoantibodies with a concomitant rise in immune complexes, whereas DVD is associated with sustained low levels of circulating immune complexes.
Identification of profound peripheral T lymphocyte immunodeficiencies in the spontaneously diabetic BB rat.
Authors: Elder M E , Maclaren N K 
Published: December 2022

Abstract
The BB rat is presently the best available animal model for human insulin dependent diabetes (IDD). Because of the extreme susceptibility of the strain to opportunistic infections and because current studies suggest that they have an autoimmune diathesis, of which IDD is but one result, aspects of the immune system of the BB rat were studied. Severe T lymphopenia was observed in all BB rats, irrespective of sex or the presence of IDD, while numbers of B cells and serum immunoglobulin levels were normal. Both the helper T lymphocyte and cytotoxic/suppressor T lymphocyte subsets, defined by reactions with monoclonal antibodies, were depressed, and an inversion of the helper T cell subset to cytotoxic/suppressor T lymphocyte subset ratio occurred in all BB rats with increasing maturity. Concomitantly, severe impairments of T cell-mediated immune responses were noted. BB rats poorly rejected allografts across both major and minor histocompatibility barriers, and BB splenic or peripheral blood lymphocytes had markedly defective proliferative responses to mitogens and to allogeneic cells in MLC. Irradiated and nonirradiated BB spleen cells did not inhibit WF mitogenic or MLC responses, which suggests that the T cell defect in BB rats is not solely due to increased suppressor activity. Because irradiated WF cells and Con A supernatants did not restore BB proliferative responses, and BB lymphocytes were able to produce IL-2 normally, a reduced ability of BB lymphocytes to respond to helper factors such as IL-2 is suggested. In contrast to T lymphocytes from spleen or peripheral blood, BB thymocytes responded as well as did WF thymocytes to Con A or Con A supernatants. Percentages of T lymphocyte subsets and histology of BB thymuses were also normal when compared to WF thymuses. However, spleens and lymph nodes from BB rats were severely depleted of T lymphocytes, and thymocytotoxic autoantibodies were detected in many BB rat sera. The above findings indicate that BB rats have T lymphocyte immunoincompetence, which appears to be a post-thymic or peripherally acquired maturational defect.
Inflammation-induced changes in rabbit CRP and plasma lipoproteins.
Authors: Cabana V G , Gewurz H , Siegel J N 
Published: December 2022

Abstract
Inflammation is accompanied by changes in the plasma concentrations of "acute phase reactants" including the C-reactive proteins of man and other species. Previous results in our laboratory showed that CRP in rabbit acute phase serum may circulate in association with very low density lipoproteins (VLDL), which influence both the apparent m.w. and electrophoretic mobility of CRP. We now show that the ability of VLDL to interact with CRP varies with time during the acute phase response. Before the induction of inflammation, the factor(s) responsible for the beta-mobility of CRP is present at low levels in the VLDL. During the first 24 hr of the acute phase response, the activity can no longer be demonstrated in the VLDL fraction. By 36 to 48 hr after inflammatory stimulation, a significantly increased level of this factor(s) is measurable in VLDL. Furthermore, during the acute phase response, the alpha-lipoproteins decrease, and the beta- and pre-beta lipoproteins increase. The increase in beta- and pre-beta-lipoproteins is due to an accumulation of VLDL isolated at d less than 1.006 g/ml. These changes are accompanied by marked hypertriglyceridemia and a significant increase in phosphocholine-containing phospholipids. A non-CRP apoprotein present in low amounts in VLDL from normal rabbit plasma appears to increase in VLDL as inflammation progresses. This VLDL apoprotein increases in response to multiple acute phase stimuli and may be a newly recognized acute phase reactant in the rabbit.
Disparate functional properties of two interleukin 1-responsive Ly-1+2- T cell clones: distinction of T cell growth factor and T cell-replacing factor activities.
Authors: Rao A , Mizel S B , Cantor H 
Published: December 2022

Abstract
We describe the properties of two Ly-1+2- T cell clones (Ly-1.14 and Ly-1.21), which are maintained in long-term culture in the absence of other cell types. The clones require media containing a source of interleukin 1 as well as interleukin 2. They retain physiologic responses to interleukin 1, which is required for optimal production of T cell lymphokines by these clones in response to concanavalin A (Con A). The two Ly-1+2- T cell clones differ in their production of lymphokines after stimulation by Con A. The supernatant of clone Ly-1.21 promotes the proliferation of T cells maintained in long-term culture, induces antibody synthesis in cultures of B cells and antigen, and induces the differentiation of cytolytic cells in cultures of thymocytes and antigen; these assays define the properties of T cell growth factor (TCGF), T cell-replacing factor for B cells (TRF-B), and T cell-replacing factor for cytolytic cells (TRF-C), respectively. In contrast, the supernatant of clone Ly-1.14 contains only TCGF activity and does not promote antibody synthesis by B cells or differentiation of cytolytic cells from thymocytes. The results indicates that TCGF and TRF activities reside on independent, although perhaps related, molecules.
Limiting dilution analysis of T helper cell heterogeneity: a single class of T cell makes both IL 2 and IL 3.
Authors: Miller R A , Stutman O 
Published: December 2022

Abstract
We have previously described a limiting dilution assay (LDA) for estimating the frequency, in the spleens of unprimed mice, of alloantigen-responsive cells that, together with their immediate clonal progeny, can produce interleukin 2 (IL 2) in short-term culture. In this paper, we provide further evidence that the limiting cell in these cultures is, in fact, the immediate precursor of the IL 2-producing cell rather than merely a participant in a multicellular cascade that ultimately leads to production of this lymphokine. We also demonstrate the usefulness of the LDA method for estimating the frequency of the limiting cell for production of IL 3. By analyzing the supernatants of these short-term microcultures for both IL 2 and IL 3, we show that essentially all wells that produce IL 3 also produce IL 2. Furthermore, the amount of IL 2 produced in any individual well correlates strongly with the IL 3 production in the same well. Our data suggest that both these lymphokines are produced by a single class of T cell, and further that the regulatory events that control IL 2 generation in allostimulated helper cells act to control IL 3 levels in parallel.
A thymocyte-activating factor derived from glomerular mesangial cells.
Authors: Lovett D H , Ryan J L , Sterzel R B 
Published: December 2022

Abstract
The glomerular mesangium is centrally involved in immune-mediated glomerulonephritis. The mesangial cell is a mesenchyme-derived multipotential vascular pericyte, which shares several properties with macrophages. Cultured, proliferating rat mesangial cells produce a factor, mesangial cell-derived thymocyte-activating factor (MC-TAF), which physicochemically and biologically closely resembles macrophage interleukin 1. MC-TAF is heat labile, of low m.w. (approximately 15,000), and adheres to anion exchangers. MC-TAF acts to augment lectin-induced thymocyte proliferation and enhances peripheral lymphocyte production of interleukin 2. These findings suggest that a mesangial cell cytokine may interact with the cellular immune system in an antigenically nonspecific fashion to modulate immune responses in glomerular disease.
Inhibition of LPS toxicity for macrophages by metallothionein-inducing agents.
Authors: Patierno S R , Costa M , Lewis V M , Peavy D L 
Published: December 2022

Abstract
Parenteral administration of adrenal corticosteroids or particular transition metal salts are known to protect mice from the lethal effects of bacterial lipopolysaccharides (LPS). To determine if both groups of substances act through similar biologic mechanisms, their capacity to protect macrophages from the direct toxic effects of LPS was examined in vitro. When added simultaneously with LPS at culture initiation, 10 to 100 microM cortisone increased the viability of normal peritoneal macrophages as determined by trypan blue exclusion. Prednisolone and corticosterone protected LPS-treated macrophages at even lower concentrations (0.1 to 1 microM); estradiol and testosterone failed to alter cell viability at any concentration tested. Protection was dependent on de novo synthesis because inclusion of 20 nM actinomycin C1 or 1 microM cycloheximide with 10 microM corticosterone during a 4-hr pretreatment period blocked induction of the protective effect. Murine macrophages were also protected by micromolar concentrations of zinc, cadmium, mercury, and manganese, but not by calcium or lead. As was obtained with corticosteroids, heavy metal-induced protection depended on de novo RNA and protein synthesis. Because all substances that protected against LPS are known inducers of metallothionein in somatic cells, peritoneal macrophages were assayed for the presence of this unique, cytoplasmic protein. Within 2 to 8 hr, 10 microM cadmium caused three to fivefold increases in the incorporation of 35S-cysteine and in the binding of 203Hg into the TCA-soluble fraction of cell lysates that was excluded on centrifugally accelerated Sephadex G-10 columns. These results suggest macrophages may be protected from LPS-mediated cytotoxicity through synthesis of a sulfhydryl-rich, metal-binding protein. Although its mechanism of action remains unknown, it is proposed that metallothionein may function homeostatically by altering intracellular concentrations of zinc or may play a regulatory role by facilitating transfer of heavy metals among metal-requiring apoproteins.
Suppression of lipopolysaccharide-induced polyclonal B cell activation of murine spleen with heat-aggregated murine immunoglobulin G.
Authors: Saito-Taki T , Nakano M 
Published: December 2022

Abstract
The effect of heat-aggregated immunoglobulin G's (HAgg-IgGs) on bacterial lipopolysaccharide- (LPS) induced polyclonal B cell activation (PBA) was studied. HAgg-IgGs (10 micrograms/ml or more) that were added to cultures of spleen cells obtained from BALB/c mice remarkably decreased the numbers of anti-trinitrophenyl (TNP) antibody-producing cells (APC) generated by LPS in cultures. This suppressive effect was seen when HAgg-IgGs were added within 1 hr after the initiation of culture. Later addition of HAgg-IgGs did not cause any effective suppression of the generation of APC. Moreover, the spleen cells, which had been pretreated with HAgg-IgGs, washed for removal of free HAgg-IgGs, and subsequently cultured, responded poorly to LPS. HAgg-IgG2b was more effective than HAgg-IgGs, but HAgg-IgG2a did not have any suppressive effect. A similar suppressive effect was observed when HAgg-IgG2b-Fc was added into culture, whereas none was noted with IgG2b-Fab. Indomethacin (IM), known as cyclooxygenase inhibitor, could completely abrogate the suppressive effects of HAgg-IgGs on LPS-induced PBA responses when it was added to the cell cultures together with HAgg-IgGs or to the cultures of HAgg-IgGs-pretreated cells. Addition of prostaglandin E2 (PGE2) showed strong suppression of the PBA responses of spleen cell cultures that had been pretreated with HAgg-IgGs and IM, but other PG analogues showed no suppression. Thus, it would appear that PGE2 has some role in the suppression of the LPS-induced PBA response.