bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recovery of human neutrophils from complement attack: removal of the membrane attack complex by endocytosis and exocytosis.
Authors: Morgan B P , Dankert J R , Esser A F 
Published: December 2022

Abstract
Nucleated cells can resist lysis by and recover from complement attack even after formation of the potentially cytolytic membrane attack complex on the cell surface. We have found that human neutrophils resist complement lysis by the physical removal of membrane attack complexes by both endocytic and exocytic process. The latter mechanism predominates, vesiculation being detectable within 60 sec of initiating the complement cascade. Sixty-five percent of the formed complexes are removed on plasma membrane vesicles, although only 2% of the cell surface is lost. Ultrastructural examination revealed that these vesicles were covered with ring-like "classical" complement lesions. Analysis of these vesicles by gel electrophoresis indicated that C9 was present exclusively in the form of a sodium dodecyl sulfate-resistant, high m.w. complex. In contrast, the 35% of C9 that remained associated with the cells was found to be inaccessible to a C9-specific monoclonal antibody, and was partly degraded, suggesting internalization of the membrane attack complex and proteolysis of some C9 molecules. The molar ratio of C9 to C8 was 12 to 1 on shed vesicles and on recovered cells.
Lethal graft-vs-host disease across major histocompatibility barriers: requirement for leucyl-leucine methyl ester sensitive cytotoxic T cells.
Authors: Thiele D L , Charley M R , Calomeni J A , Lipsky P E 
Published: December 2022

Abstract
L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) is selectively toxic for human natural killer (NK) cells and cytotoxic T lymphocytes (CTL) at both the precursor and effector stage of differentiation. The present studies explored the effects of Leu-Leu-OMe on murine spleen cell function. Leu-Leu-OMe exposure removed NK function from murine spleen cells but spared their capacity to proliferate in response to lipopolysaccharide and Con A. The capacity to generate CTL from both L3T4 (+) and Lyt-2 (+) precursors was lost after Leu-Leu-OMe treatment, whereas alloantigen-induced proliferation and interleukin 2 (IL 2) production by L3T4 (+) T helper cells remained intact. Lethal graft vs host disease (GVHD), which developed in irradiated (C57BL/6 X DBA/2)F1 recipients of C57BL/6 bone marrow and spleen cells was completely prevented by Leu-Leu-OMe treatment of donor cells. In contrast depletion of Lyt-2 positive cells from the donor inoculum did not prevent acute GVHD in this fully major histo-compatibility complex (MHC) incompatible strain combination. However, Leu-Leu-OMe treatment of the Lyt-2 depleted inoculum completely prevented lethal GVHD, although the treated cells retained the capacity to proliferate and secrete IL 2 normally after in vitro stimulation with (C57BL/6 X DFA/2)F1 spleen cells. These findings indicate that L3T4 (+) T helper cells alone are unable to initiate lethal GVHD in this H-2 incompatible strain combination. Rather, lethal GVHD requires the transfer of a Leu-Leu-OMe sensitive T cell subset, likely to be thymus educated pre-CTL. Leu-Leu-OMe treatment should provide a useful way to delineate subpopulations of cells involved in the production of lethal GVHD and an approach to preventing this complication of bone marrow transplantation.
Demonstration of a calcium influx in cytolytic T lymphocytes in response to target cell binding.
Authors: Gray L S , Gnarra J R , Engelhard V H 
Published: December 2022

Abstract
By using the Ca2+-sensitive dye indo-1, an antigen-specific increase in intracellular Ca2+ in cloned cytolytic T lymphocytes (CTL) was measured under conditions that were permissive for T cell-mediated cytolysis. To synchronize lethal hit delivery in a suspension of effector and target cells, a modification of the cation pulse method in which Ca2+ is added to preformed conjugates of CTL and target cells was used. Conjugate formation was unaffected by the absence of extracellular Ca2+ under these conditions. Lytic activity of these cloned CTL was markedly reduced in the absence of extracellular Ca2+ and was restored upon Ca2+ repletion. When indo-1-loaded CTL were preincubated with target cells in the absence of extracellular Ca2+, a marked antigen-specific increase in indo-1 fluorescence, indicative of an increase in intracellular Ca2+, was observed after repletion of extracellular Ca2+. This increase in intracellular Ca2+ was shown to be due solely to changes in the CTL and not the target cell within the time course of the experiment, and results from the influx of extracellular Ca2+. Antibody to the T cell receptor for antigen also evokes a similar increase in intracellular Ca2+ in CTL under these conditions. This method provides a means for the direct examination of the response of CTL to cellular antigen as well as soluble antibody and is a versatile and valuable tool for the study of CTL function.
Selective inhibition of the generation of T suppressor cells of contact sensitivity in vitro by interferon.
Authors: Knop J , Taborski B , DeMaeyer-Guignard J 
Published: December 2022

Abstract
The T suppressor (Ts) cell response in contact sensitivity is preferentially inhibited by murine interferon-alpha, beta (IFN-alpha, beta) in vivo. Previous studies in vivo have suggested that IFN exerts its effect directly on the Ts subpopulation rather than through an effect on antigen-presenting macrophages. Nevertheless, the mechanism of this selective blockade remained unclear. To better define the mechanism(s) of inhibition of suppression by IFN-alpha, beta, we determined whether IFN acted on lymphocytes, macrophages, or both. Antigen-specific T effector cells of delayed-type hypersensitivity (TDH) and Ts cells were induced in vitro by co-culture of spleen lymphocytes with bone marrow-derived antigen-presenting macrophages (BM-MA) pulse-labeled with 2,4-dinitrobenzene sulfonate (DNBSO3). TDH or Ts activity was demonstrated by transfer of the lymphocytes into naive recipient BALB/c mice after 3 days of culture. BM-MA cultured for 5 to 7 days (BM-MA d5-7) before labeling preferentially activated TDH cells (Thy-1+, Lyt-1+2-); 10- to 14-day-old BM-MA (BM-MA d10) induced Ts cells (Thy-1+, Lyt-2+), as previously shown. Treatment of the spleen lymphocyte suspension with pure mouse IFN-alpha, beta at a dose of 10(3) U/10(8) cells completely blocked the induction of Ts cells but had no effect on the induction of TDH cells. Pretreatment of the antigen-presenting BM-MA for 24 hr with IFN (10(2) U/3 X 10(5) cells) had no effect on the induction of Ts and TDH cells. Cultivation of lymphocytes on a DNP-BM-MA d6 monolayer did not result in the induction of Ts cells; however, in the presence of a goat anti-murine IFN-alpha, beta antibody, Ts cells were induced. This finding indicates that the spontaneous release of IFN-alpha, beta in those cultures prevented the induction of Ts cells. These results confirm our previous observation that Ts cells are more easily blocked by IFN-alpha, beta than TDH cells, and demonstrate that IFN affects the Ts subpopulation not via modulation of the antigen-presenting macrophages. IFN-alpha, beta-producing, antigen-presenting, or accessory cells may therefore prevent the activation of this type of Ts cell.
Lack of expression of HLA [corrected] class I and class II molecules on the human oocyte.
Authors: Dohr G A , Motter W , Leitinger S , Desoye G , Urdl W , Winter R , Wilders-Truschnig M M , Uchanska-Ziegler B , Ziegler A 
Published: December 2022

Abstract
The expression of histocompatibility leukocyte antigen (HLA) class I and class II antigens on human oocytes was investigated by the indirect immunofluorescence assay using well-defined monoclonal antibodies. Oocytes were obtained from an in vitro fertilization program or were studied on frozen sections from human ovaries. Neither HLA class I, beta 2-microglobulin, nor HLA class II molecules were detected on cultured oocytes or frozen sections. The zona pellucida also lacked these antigens, but granulosa cells expressed HLA class I molecules. Our results also indicate the presence of certain types of class II molecules on granulosa cells. The present experiments demonstrate that the human oocyte belongs to those few cell types in the human body which are devoid of both types of HLA molecules.
Down-regulation of interleukin 1 production by macrophages of sarcoma-bearing mice.
Authors: Moldawer L L , Lonnroth C , Mizel S B , Lundholm K G 
Published: December 2022

Abstract
Peritoneal macrophages from mice bearing a transplantable methylcholanthrene-induced sarcoma produced progressively less IL 1 as tumor burden increased. The loss of activity was not explained by the production of any inhibitor of the mouse thymocyte comitogen bioassay. Immune precipitation with a polyclonal antibody confirmed the decline in IL 1 appearance. Although tumor-bearing animals lost approximately 17% of their carcass mass, the reduced production of IL 1 was not satisfactorily explained by coexistent malnutrition, since similarly depleted non-tumor-bearing mice were capable of producing IL 1. In addition to an altered IL 1 production by macrophages of tumor-bearing mice, SDS-polyacrylamide gel electrophoresis and autoradiography revealed that the pattern of secretory protein synthesis from LPS-stimulated and unstimulated peritoneal macrophages differed between tumor-bearing and control animals. Administration of LPS to tumor-bearing mice early after tumor transplantation resulted in reduced tumor growth and prevented the down-regulation of in vitro IL 1 production by peritoneal macrophages. These findings demonstrate a specific defect in IL 1 production associated with increasing tumor burden. Further studies are required to determine whether this defect in IL 1 synthesis contributes to the increased tumor growth.
Structure of the T15 VH gene subfamily: identification of immunoglobulin gene promotor homologies.
Authors: Siu G , Springer E A , Huang H V , Hood L E , Crews S T 
Published: December 2022

Abstract
We have sequenced and analyzed the flanking and coding regions of four closely related mouse VH gene segments referred to as the T15 gene subfamily. We have found that although the sequence homologies between the four members of this family are greatest in the coding region, significant homologies extend into the leader sequences and the flanking regions as well. Sequence comparisons of the promoter regions of other VH gene segments indicate that the octamer promoter sequence is part of a larger conserved sequence that may play an important role in immunoglobulin gene transcription. Analysis of the lambda clones containing the members of this subfamily indicate that despite the close linkage of two of the members, the average number of kilobases of DNA between the germ-line gene segments of this family is likely to be very great.
The correlation of lectin-stimulated proliferation and cytotoxicity in murine thymocytes with expression of the MEL-14-defined homing receptor.
Authors: Wilson A , Scollay R , Reichert R A , Butcher E C , Weissman I L , Shortman K 
Published: December 2022

Abstract
The relationship between the expression of the MEL-14-defined lymphocyte homing receptor and the proliferation and functional differentiation of thymocytes in response to lectin stimulation was examined. Two-color fluorescent staining with MEL-14 in various combinations with PNA and anti-Ly-2 and anti-L3T4 was used to separate thymocyte populations for functional analysis. A high cloning-efficiency limit-dilution culture system was used to determine the frequency of all cells responsive to concanavalin A (PTL-p) or of all precursors of lectin-enhanced cytolytic lymphocytes (CTL-p). As expected from earlier studies, PTL-p and CTL-p were concentrated in the PNA- thymocytes, PTL-p were in both the Ly-2- L3T4+ and the Ly-2+ L3T4- subpopulations, and CTL-p were predominantely in the Ly-2+ L3T4- subpopulation. Within the PNA- thymocytes, two distinct peaks of PTL-p were found in cells stained with MEL-14, corresponding to MEL-14- and MEL-14medium-to-high cells, whereas the CTL-p frequency increased in fractions showing increasing expression of the MEL-14-defined antigen. Within the Ly-2- L3T4+ subpopulation, two distinct peaks of PTL-p were found corresponding to groups of MEL-14- and MEL-14medium-to-high cells, with the intermediate fraction of MEL-14low cells displaying a very low PTL-p frequency. The Ly-2+ L3T4- subpopulation included fewer MEL-14- cells and more MEL-14high cells than the Ly-2- L3T4+ subpopulation. Within the Ly-2+ L3T4- subpopulation, the few MEL-14- cells expressed a relatively low but definite frequency of CTL-p and PTL-p. The more numerous MEL-14+, Ly-2+ L3T4- cells included a high frequency of CTL-p and PTL-p, which did not vary over the medium-to-high MEL-14 expression range. These results indicate that the correlation of MEL-14 expression with CTL-p frequency among thymocytes is largely a consequence of the relative frequency of Ly-2+ L3T4- cells in the separated fractions, rather than a direct link between MEL-14 expression and function. Nevertheless, MEL-14 does define significant heterogeneity in both the Ly-2+ L3T4- and the Ly-2- L3T4+ subpopulations. In particular, there is a reduced functional response among the small subgroup of Ly-2+ L3T4- MEL-14- cells, suggesting this population includes either immature cells or cells of a different functional type.
Human monocyte or recombinant interleukin 1's are specific for the secretion of a metalloproteinase from chondrocytes.
Authors: Schnyder J , Payne T , Dinarello C A 
Published: December 2022

Abstract
Macrophage products induce production of proteases that contribute to cartilage degradation in various joint diseases. In these studies we stimulated rabbit chondrocytes with various cytokines in vitro in order to determine which were responsible for changes in the release of prostaglandin, plasminogen activator, and a metalloproteinase. The metalloproteinase assayed in these studies is a latent enzyme whose activity can rapidly be measured with fluorogenic casein. Conditioned media from stimulated human peripheral blood mononuclear cells; purified human monocyte IL 1, pI 7,6, and 5; and recombinant human IL 1, beta or alpha forms, all changed the secretory pattern of rabbit articular chondrocytes in a similar manner: production and secretion of a latent metalloproteinase(s) and prostaglandin E were stimulated in a concentration-dependent fashion, whereas the activity of plasminogen activator was strongly reduced. Antibodies against human monocyte IL 1 blocked the active principle in various mononuclear cell-conditioned media, suggesting that uncharacterized factors present in these supernatants do not affect the metalloproteinase response. When added to confluent chondrocytes, phorbol myristate acetate, concanavalin A, IL 2, lipopolysaccharide, indomethacin, and prostaglandin E2, which interfere with lymphocyte proliferation assays for IL 1, failed to influence chondrocyte metalloproteinase secretion. Recombinant human IFN-alpha or IFN-gamma in the presence or absence of IL 1 had no effect on rabbit chondrocytes, whereas recombinant human tumor necrosis factor decreased plasminogen activator but had no effect on prostaglandin or metalloproteinase production. These results support the concept that IL 1 specifically induces chondrocytes to produce metalloproteinases, and hence may play an important role in destructive joint diseases.
The glycine-alanine repeating region is the major epitope of the Epstein-Barr nuclear antigen-1 (EBNA-1).
Authors: Rumpold H , Rhodes G H , Bloch P L , Carson D A , Vaughan J H 
Published: December 2022

Abstract
The Epstein-Barr nuclear antigen-1 (EBNA-1) is a protein containing a large glycine-alanine repeat that has been shown to be antigenic. Antibodies to EBNA-1 can be detected by means of immunoblotting. Preincubation of antisera with purified EBNA-1 protein inhibits the binding of IgG antibodies in this system, indicating that those epitopes detected by immunoblots are also accessible on the native molecule. A number of synthetic peptides the sequences of which were derived from the glycine-alanine repeating region of EBNA-1 and from regions adjacent to it also inhibited antibody binding to EBNA-1. These showed, however, a 1000-fold variation in their inhibitory activities. Peptides containing only glycine and alanine were the most effective inhibitors. The anti-EBNA-1 antibodies did not react with several other peptides representing sequences from unrelated proteins. At saturating concentrations of peptide 85 to 100% of anti-EBNA-1, antibody binding was inhibited in all sera tested with one exception. Similar results are obtained when antibody binding is assayed by an enzyme immunosorbent assay by using partially purified EBNA-1 to coat the plates. Thus the glycine-alanine region, either through its primary structure or through conformations assumed by this region, forms the major epitope(s) of the EBNA-1 molecule.
Changes in gene expression induced by a phorbol diester: expression of IL 2 receptor, T3, and T cell antigen receptor.
Authors: Shackelford D A , Smith A V , Trowbridge I S 
Published: December 2022

Abstract
Phorbol esters cause an apparent differentiation of human T leukemic cell lines. It was shown previously that TPA induces the expression of the interleukin 2 (IL 2) receptor and the T3 complex on some T cell lines, including CCRF-CEM. We demonstrate that expression of the IL 2 receptor correlated with an induction of the 3.5 and 1.5 kb IL 2 receptor mRNA. In addition, the TPA-induced expression of the T3 polypeptides was found to be accompanied by induction of a putative T cell antigen receptor heterodimer on CEM cells. This was demonstrated by the co-precipitation of the T cell receptor with T3 from digitonin-solubilized cells. The cells expressed high levels of T3 delta- and T cell receptor beta-chain mRNA in the absence of TPA. The effect of TPA was to cause a rapid accumulation of T cell receptor alpha-chain mRNA. This suggested that the alpha-chain gene was rearranged before TPA induction and that expression of the T cell receptor/T3 complex on the cell surface was regulated by the level of alpha-chain expression. It was also shown that cloned sublines of CEM cells which expressed different T cell antigen phenotypes differed in their response to TPA.
Cortical thymocyte differentiation in thymomas: an immunohistologic analysis of the pathologic microenvironment.
Authors: Takacs L , Savino W , Monostori E , Ando I , Bach J F , Dardenne M 
Published: December 2022

Abstract
Four monoclonal antibodies (BH11, T2/30, AG3, and BC3) were produced against different epithelial components of the normal thymus. An immunohistologic study was performed on 13 thymomas by the use of these and other stromal and lymphocyte-specific reagents. The aim of this study was to find possible relationships between the proliferating thymoma epithelial cell type and the T cell composition of thymomas. Our results indicate that cortical T cell differentiation is present in thymomas, and that this differentiation is induced in the absence of detectable levels of MHC class II antigens on the epithelial component in most cases. The role of the MHC class II antigens cannot be excluded, however, because these antigens were always present on macrophages. Analysis of the selected group of thymomas, each of which contained epithelial cells homogeneously stained by at least one of the described monoclonal antibodies, showed that the cortical type T cell inducer capacity of thymomas is independent of the epithelial type predominant in the tumor.
Lymphoid tissue- and inflammation-specific endothelial cell differentiation defined by monoclonal antibodies.
Authors: Duijvestijn A M , Kerkhove M , Bargatze R F , Butcher E C 
Published: December 2022

Abstract
Endothelial cells play an essential role in immune responses by regulating the entry of leukocytes into lymphoid tissues and sites of inflammation. As an initial approach to analyzing endothelial cell specialization in relation to such immune function, we have produced monoclonal antibodies (MAB) against mouse lymph node endothelium. Three antibodies were selected: MECA-20, recognizing the endothelium of all blood vessels in lymphoid as well as non-lymphoid organs; MECA-217, which stains the endothelium lining large elastic arteries, but among small vessels is specific for post-capillary venules within lymphoid organs and tissues exposed to exogenous antigen, such as skin and uterus; and MECA-325, an antibody that demonstrates specificity for the specialized high endothelial venules (HEV) that control lymphocyte homing into lymph nodes and Peyer's patches. MECA-325 failed to stain vessels in any non-lymphoid organs tested. Immunoperoxidase studies of HEV in lymph node frozen sections, and of isolated high endothelial cells in suspensions, demonstrated that the antigens recognized by all three antibodies are expressed at the cell surface; those defined by MECA-20 and MECA-325 are also present in the cytoplasm. To study the regulation of the antigens defined by these MAB in relation to extra-lymphoid immune reactions, we assessed their expression in induced s.c. granulomas as a model for chronic inflammation. Small vessels in the granulomas were already stained by MECA-217 in the first days of development. In contrast MECA-325 detected postcapillary venules (which frequently displayed the morphologic characteristics of HEV) only from approximately 1 wk, in parallel with the development of a persistent mononuclear cell infiltrate including numerous lymphocytes. The selective appearance of the MECA-325 antigen on vascular endothelium supporting lymphocyte traffic in both lymphoid and extra-lymphoid sites suggests that this antigen may play an important role in the process of lymphocyte extravasation. The demonstration of lymphoid organ- and inflammation-specific microvascular antigens offers direct evidence for a complex specialization of endothelium in relation to immune stimuli, and supports the concept that microvascular differentiation may play an important role in local immune responses.
Terminal complement components play a role in the expression of C5a.
Authors: Gresham H D , Renfer L , Hammer C H , Frank M M 
Published: December 2022

Abstract
This study examined the expression of C5a detected antigenically (RIA) and functionally (PMN-myeloperoxidase release) consequent to classical or alternative pathway convertase cleavage. Maximal C5a expression occurred when C5 was cleaved in the presence of the later-acting complement components, C6, C7, and C8. This effect was detected by using both purified components and normal human serum immunochemically depleted of C7 or C8 and reconstituted with the purified component. C6 alone was not sufficient to augment C5a expression. Subsequent incubation of C6 and C7 with C5 cleaved in the absence of the terminal components was not sufficient for C5a release. Repeated freezing and thawing of C5 cleaved in the absence of C6 and C7 produced C5a equivalent to that detected when convertase cleavage occurred in the presence of the terminal components. Mild detergent treatment of convertase-cleaved C5 was not sufficient for C5a release. We believe that these data indicate a role for the terminal complement components in the expression of both C5a antigen and function. The mechanism for this effect is not known, but it may involve conformational changes in the C5 molecule that occur during membrane attack complex formation.