bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contributions of the Mac-1 glycoprotein family to adherence-dependent granulocyte functions: structure-function assessments employing subunit-specific monoclonal antibodies.
Authors: Anderson D C , Miller L J , Schmalstieg F C , Rothlein R , Springer T A 
Published: December 2022

Abstract
MAb directed at the alpha-subunits of Mac-1 (alpha M), LFA-1 (alpha L), p150,95 (alpha X), or their common beta-subunit were used to characterize the contributions of the Mac-1 glycoprotein family to granulocyte adherence reactions. Inhibitory effects of these MAb in incubation experiments with normal granulocytes indicated distinct adhesive contributions of each subunit. Significantly greater adherence, and inhibition of adherence by anti alpha M, alpha X, and beta MAb, was observed under chemotactic conditions designed to "up-regulate" the surface expression of the alpha M beta and alpha X beta complexes. Adherence to protein-coated glass and binding of albumin-coated latex beads were significantly inhibited by anti-beta greater than anti-alpha M (OKM-10, M1/70, LM2/1.6 and OKM-1) greater than anti-alpha X greater than anti-alpha L MAb, but no effects of anti-HLA, AB, or anti-CR-1 MAb were evident. A similar rank order of inhibition was observed in granulocyte aggregation assays in response to C5a, PMA, or f-Met-Leu-Phe. Significant inhibition of directed migration by anti-beta or anti-alpha M (OKM-1 or OKM-10) MAb was observed in subagarose but not Boyden chemotaxis assays; inhibition was dependent on a continuous cell exposure to anti-Mac-1 alpha or beta during the assay, suggesting that a continuum of new Mac-1 expression is required for directed translocation. Phagocytosis of Oil-Red-O paraffin or zymosan selectively opsonized with C3-derived ligands was significantly inhibited by anti-alpha M MAb (OKM-10 greater than LM2/1.6 greater than M1/70 greater than OKM-1) or by combinations of anti-alpha M + anti-CR-1 MAb, but only minimal inhibitory effects of anti-beta MAb and no effects of anti-alpha L or anti-alpha X MAb were seen. Similarly, complement-dependent phagocytosis-associated lactoferrin release, ingestion, and intracellular killing of Staphylococcus aureus 502A, and binding of iC3b-opsonized SRBC, were significantly inhibited by anti-alpha M (OKM-10, M1/70) or combinations of anti-alpha M + anti-CR-1 MAb, but not by anti-beta, alpha L, or alpha X MAb. Notably, none of the anti-Mac-1 MAb demonstrated inhibitory effects in assays of adherence-independent functions including shape change, specific f-Met-Leu-3H-Phe binding, O-2 generation, chemiluminescence evolution, or lactoferrin release in response to PMA.(ABSTRACT TRUNCATED AT 400 WORDS)
Interleukin 2 receptors on cultured murine epidermal Langerhans cells.
Authors: Steiner G , Tschachler E , Tani M , Malek T R , Shevach E M , Holter W , Knapp W , Wolff K , Stingl G 
Published: December 2022

Abstract
Rat monoclonal antibodies 3C7 and 7D4 detect two distinct functional regions of the murine interleukin 2 (IL 2) receptor. When studying the emergence kinetics of IL 2 receptors in mixed epidermal cell (EC)-lymphocyte cultures by using 3C7 and 7D4 in an indirect immunofluorescence assay, we regularly encountered a distinctive membrane fluorescence not only on lymphocytes, but also on a subpopulation of cells exhibiting a dendritic morphology. Reasoning that these 3C7/7D4-reactive dendritic cells might represent a subpopulation of epidermal dendritic cells, we studied mouse EC for the presence of 3C7/7D4- reactive cells. Although 3C7/7D4 reactivity was never detected on freshly isolated EC or on epidermal sheets, a small number of 3C7/7D4+ cells was encountered after 24 to 48 hr of culture. These cells exhibited a dendritic shape, expressed Ia antigens, lacked Thy-1 antigens, and displayed the ultrastructural features of Langerhans cells (LC) with the notable exception of Birbeck granules. Although after 24 hr, only 20% of Ia+ EC were 3C7/7D4+, the vast majority of LC displayed 3C7/7D4 binding sites after 4 to 5 days of culture. Preincubation of cultured LC-enriched EC with recombinant human IL 2 prevented subsequent 3C7-but not 7D4-binding to these cells. Western blot analysis of 7D4-reactive material of detergent extracts from LC-enriched EC revealed three bands in the same m.w. range as reported for CTLL cells. These results demonstrate that cultured LC express IL 2 receptors and may bear important implications for a better understanding of growth regulation, differentiation, and immunologic functions of LC.
Monocyte-mediated augmentation of human natural killer cell activity: conditions, monocyte and effector cell characteristics.
Authors: Bloom E T , Babbitt J T , Kawakami K 
Published: December 2022

Abstract
The characteristics of the effector cells and monocytes, and conditions required for the monocyte-mediated augmentation of human natural killer (NK) cell activity were investigated. Enriched null cell populations were further fractionated by Percoll centrifugation and used as effector cells. The LGL-enriched fraction was less susceptible than either the unfractionated cells or the other Percoll fractions to the monocyte augmentation when mixed with monocytes in the chromium-release assay and when precultured with monocytes for 12 hr, retrieved by carbonyl iron treatment, and tested for NK activity against K562. This differential susceptibility was reflected at the single cell level. The LGL-enriched Percoll fraction did not display the increase in target-binding cells with lytic activity that was exhibited by the other effector cell preparations after culture with monocytes. No differences in Leu-7 and Leu-11 phenotypes were detected between enriched null cells that had been cultured with and without monocytes for 12 hr. At the monocyte level, it was shown that pretreatment of the monocytes with LPS did not alter their NK-augmenting activity appreciably. Glutaraldehyde-fixed monocytes were not effective, and actinomycin D-treated monocytes were less effective than untreated or irradiated monocytes when mixed with enriched null cells in the assay. Actinomycin D-treated monocytes did not augment and possibly suppressed NK activity tested after 12-hr culture, and irradiated monocytes were less effective for augmenting NK activity than untreated cells. Monocyte-mediated augmentation could be detected when the medium used for null cell-monocyte coculture was supplemented with a) different lots of fetal bovine serum, b) human AB serum, c) autologous serum, or d) no serum. Polymyxin B and indomethacin did not alter the monocyte effect. Finally, the monocyte-mediated augmentation of human NK was not MHC restricted, since allogeneic combinations were also effective. These results suggest that 1) lymphocytes other than LGL participate in the monocyte-mediated augmentation of NK activity, 2) the augmentation is probably activational rather than maturational, 3) the monocytes must be viable to be effective when mixed with null cells during the assay, 4) de novo RNA and/or protein synthesis by the monocytes is required for the monocytes to induce augmented activity in null cells after 12-hr coculture, 5) prostaglandin synthesis and endotoxin are probably not involved in the augmentation, 6) the phenomenon is not MHC restricted, and 7) monocytes may express augmentative and suppressive activities concurrently.
Enteral and systemic release of leukotrienes during anaphylaxis of Nippostrongylus brasiliensis-primed rats.
Authors: Moqbel R , King S J , MacDonald A J , Miller H R , Cromwell O , Shaw R J , Kay A B 
Published: December 2022

Abstract
Rats with acquired immunity to the intestinal nematode Nippostrongylus brasiliensis develop anaphylaxis after i.v. challenge with an extract of worm antigen, with the small intestine being the primary shock organ. In the present study we have shown that these events were associated with significant elevations in intestinal and plasma concentrations of leukotrienes LTB4 and LTC4. The changes were observed in immune rats over 10-, 30-, and 60-min intervals after antigen challenge but were absent in control animals. These lipid mediators were identified both in the perfusate of the gut lumen, which contained large quantities of mucus, and in homogenates of intestinal tissue. In addition, significant elevations in the concentrations of plasma LTB4 and LTC4 were detected in immune challenged rats but not in controls. Leukotrienes were identified by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography (RP-HPLC). RP-HPLC analysis of SRS-A leukotrienes in immune challenged rats indicated that LTC4 was the predominant sulfidopeptide leukotriene at 10 min, with almost complete biodegradation to LTD4 and LTE4 within 30 min. Infected rats also had significant increases in the numbers of intestinal mucosal mast cells (MMC) and eosinophils. Evidence of MMC activation during anaphylaxis was obtained by showing significant elevations of intestinal and systemic concentrations of their exclusive serine enzyme, rat mast cell proteinase II (RMCPII). Thus, the release of substantial amounts of leukotrienes in the gut and plasma of N. brasiliensis-primed rats after interaction with worm antigens suggests that these potent mediators may play an important role in allergic-type hypersensitivity known to occur during immune reactions against parasitic helminths.
Immune response to the pre-S(1) region of the hepatitis B surface antigen (HBsAg): a pre-S(1)-specific T cell response can bypass nonresponsiveness to the pre-S(2) and S regions of HBsAg.
Authors: Milich D R , McLachlan A , Chisari F V , Kent S B , Thorton G B 
Published: December 2022

Abstract
Hepatitis B surface antigen (HBsAg) particles are composed of a major polypeptide, p25, and additional polypeptides of higher m.w., namely p33 and p39, are variably present. All three polypeptides share the 226 amino acid residues of the S region: p33 consists of the p25 sequence plus an NH2-terminal 55 residues (pre-S(2], and p39 consists of the p33 sequence plus an NH2-terminal 108-119 residues (pre-S(1). In previous studies we demonstrated the influence of two Ir genes on the humoral and cellular immune responses to the S region and identified nonresponder phenotypes (H-2f,s). Subsequent studies showed that the immune response to the pre-S(2) region was regulated by H-2-linked genes independently of the S region response, such that immunization of S region nonresponder, pre-(S2) region responder mice (H-2s) with HBsAg/p33 circumvented nonresponse to the S region. In the present study, we have extended this analysis to the pre-S(1) region of HBsAg, with the following results: 1) and pre-S(1) region is immunogenic at the T and B cell levels; 2) anti-pre-S(1) specific antibody production is regulated by H-2-linked genes and can be independent of anti-S and anti-pre-S(2) antibody production; 3) immunization of H-2f strains with HBsAg/p39 particles containing the pre-S(1) region can bypass nonresponsiveness to the S and pre-S(2) regions in terms of antibody production; 4) two synthetic peptides, p32-53 and p94-117, define murine and human antibody binding sites on the pre-S(1) region, and p1-21 and p12-32 define additional human antibody binding sites; 5) pre-S(1)-specific T cells can be elicited in S and pre-S(2) region nonresponder mice (H-2f) and provide functional T cell help for S-pre-S(2)-, and pre-S(1)-specific antibody production; and 6) a T cell recognition site in the pre-S(1) region, p12-32 was identified. These results are relevant to HBV vaccine development, and possibly to viral clearance mechanisms, since the higher m.w. polypeptides are preferentially expressed on intact virions.
Cellular control of abscess formation: role of T cells in the regulation of abscesses formed in response to Bacteroides fragilis.
Authors: Shapiro M E , Kasper D L , Zaleznik D F , Spriggs S , Onderdonk A B , Finberg R W 
Published: December 2022

Abstract
Although abscesses are a major sequela of infection, little is known about which cellular events initiate and which prevent this pathologic response. These studies are the first to indicate a role for T cells in the important pathogenic process of abscess development and also in immunity to abscesses induced by Bacteroides fragilis. We have shown that T cells initiate the formation of abscesses in mice after i.p. challenge with B. fragilis. These T cells bear both Ly-1 and Ly-2 surface markers. Nude mice (which have been shown by others to have T cell or T cell precursors) are also able to form abscesses. Cyclophosphamide-treated mice (with depressed T cell function) were not capable of developing abscesses. Reconstitution with normal or nude mouse spleen cells restored this ability. However, reconstitution with anti-Thy-1.2-treated, anti-Ly-1, or anti-Ly-2-treated spleen cells (or a mixture of the two cell populations) failed to allow abscess formation after bacterial challenge. Immunity to abscesses caused by B. fragilis requires two T cells. The first Ly-1-2+ T cell has an IJ surface marker and has been shown to release a small m.w. soluble factor (ITF) that is antigen specific. Immunity to abscesses, however, depends on the interaction of ITF with a second Ly-1-2+ T cell, demonstrated in reconstitution experiments with nude mice. The data presented document a critical role for T cells in abscess induction and suggest the existence of a suppressor-like T cell circuit in immunity to abscesses.
Effect of an inhibitor of DNA methylation on T cells. I. 5-Azacytidine induces T4 expression on T8+ T cells.
Authors: Richardson B , Kahn L , Lovett E J , Hudson J 
Published: December 2022

Abstract
Maturing thymocytes express a series of cell surface glycoproteins which can be identified by monoclonal antibodies. The stage II or common thymocyte expresses the phenotype T4+T8+T6+T3-. In response to unknown signals, but presumably involving interactions with products of the major histocompatibility complex, the thymocyte suppresses either the T8 or T4 gene, becoming committed to the T4+T8- or T4-T8+ phenotype. With maturation, the thymocyte also becomes T6-T3+. To study whether DNA methylation may be involved in regulating expression of these determinants in mature T cells, we treated cloned interleukin 2-dependent T8- and T4-bearing T cells with 5-azacytidine (5-azaC), a nucleoside analog which inhibits methylation of newly synthesized DNA. In this report, we show that T8+ T cells treated with 5-azaC express the phenotype T8+T4+T6-T3+. Treatment of the same cells with hydroxyurea, an inhibitor of DNA synthesis, failed to induce T4 on T8+ cells. These results suggest that expression of the T4 gene may be suppressed by DNA methylation in mature T8+ cells.
Persistence of polyclonal B cell activation with undetectable parasitemia in late stages of experimental Chagas' disease.
Authors: d'Imperio Lima M R , Eisen H , Minoprio P , Joskowicz M , Coutinho A 
Published: December 2022

Abstract
The polyclonal B cell responses induced by Trypanosoma cruzi infection last for at least 6 mo after the inoculation of the parasites. In the acute phase of the disease, B cells from spleen and lymph nodes are largely stimulated, whereas a decrease in bone marrow PFC is observed. As the disease progresses, the numbers of Ig-secreting cells in the spleen, lymph nodes, and bone marrow are all enhanced. The isotype distribution of PFC, however, remains unvariable along the course of the infection, and it is characterized by the predominance of IgG2a- and IgG2b-secreting cells. No striking difference in the isotype pattern of resistant and susceptible strains of mice was observed. The continuous and long-lasting B cell stimulation generated during the infection may have important consequences in the pathology of Chagas' disease.
T cell-induced expression of membrane IgG by 70Z/3 B cells.
Authors: Jacobs D H , Sneller M C , Misplon J A , Edison L J , Kunimoto D Y , Strober W 
Published: December 2022

Abstract
To study T cell regulation of B cell isotype differentiation, we determined the capacity of clonal T cell populations (hybridomas derived by fusing BW5147 with Con A-activated Peyer's patch (PP) and spleen T cells) to induce "downstream" isotype expression by the pre-B cell lymphoma 70Z/3. In initial studies, we found that 70Z/3 B cells cultured in the presence of LPS (1 microgram/ml) expressed membrane IgM (mIgM) but not membrane IgG (mIgG). In contrast, 70Z/3 B cells cultured with HAJ-3 T cells, a PP-derived T cell hybridoma (as well as other similarly derived PP and spleen hybridomas), or with HAJ-3 T cells plus LPS do express mIgG. Such expression occurred in spite of mitomycin C-induced blockage of cell proliferation, and is observed in 70Z/3 B cell subclones cultured with HAJ-3 T cells. For these reasons, it is not due to selective expansion of a small pre-switched mIgG-bearing 70Z/3 B cell subpopulation. In other studies it was shown that 70Z/3 B cells expressing mIgG after induction by HAJ-3 T cells continue to express mIgM and do not secrete IgG. Finally, exposure of 70Z/3 B cells to the macrophage factor IL 1 and the T cell factors IL 2, BSF-pl, and BCGF-II present in EL-4 cell supernatants did not result in mIgG expression. On the basis of these studies, we conclude that a clonal B cell population expressing mIgM can be induced by T cells to co-express mIgG. Because the B cells do not express mIgG unless exposed to T cells, this represents a T cell-induced isotype switch.
Derivation of cytotoxic T cell lines that express T cell receptor but exhibit reversible loss of stable antigen binding.
Authors: Gnarra J R , Engelhard V H 
Published: December 2022

Abstract
Stable cell lines lacking cytotoxic activity against specific target cells were derived from highly active murine CTL clones by the omission of antigen from the culture for several weeks. Several independent CTL clones cultured in the absence of antigen showed a gradual decline in cytotoxic activity, resulting in complete loss by 5 to 10 wk. Such noncytotoxic (NC) cells lacked the ability to form stable conjugates with specific target cells, but were able to kill all target cells tested in the presence of Con A. It was shown by subcloning at limiting dilution that all cells in the starting population were cytolytically active, and that all cells in the NC population derived from such a clone were cytolytically inactive against target cells bearing an appropriate antigen under normal assay conditions. By using the monoclonal antibody F23.1, which reacted with the antigen receptors of two of the CTL clones, it was shown that the NC cells derived from these clones continued to express the receptor at normal levels. Levels of expression of Thy-1.2, Lyt-2.2, and LFA-1 were also similar in all cytotoxic cell lines and their noncytotoxic derivatives. The F23.1 antibody induced an increase in cytoplasmic free Ca2+ in both CTL and NC cells, and NC cells lysed F23.1 hybridoma cells in the absence of Con A. When cells expressing appropriate target cell antigen were added back to cultures of NC cells, cytotoxic activity of appropriate specificity was fully recovered in 2 wk. These results indicate that expression of an apparently functional antigen receptor alone is insufficient for stable binding of CTL to specific target cells, and that other factors dependent upon antigen stimulation may be involved in the recognition process. A difference in affinity for antigen between CTL and NC cells is suggested as a possible explanation for these observations.
Accessory cells in immune suppression. III. Evidence for two distinct accessory cell-dependent mechanisms of T lymphocyte-mediated suppression.
Authors: Moser G , Cheng G , Abbas A K 
Published: December 2022

Abstract
Suppression of antibody secretion by the 2,4,6-trinitrophenol (TNP)-binding BALB/c myeloma, MOPC 315, by idiotype- and hapten-reactive suppressor T cells is mediated by secreted factors (TsF) and requires the presence of accessory cells (AC). Idiotype-specific TsF functions only in the presence of Ia+ AC and is completely idiotype specific. Moreover, no suppression is observed when myeloma targets and AC are separated by cell-impermeable membranes, indicating that the role of AC may be to bind, focus, and/or present TsF to the myeloma cells. In contrast, TNP-specific TsF inhibits myeloma function in the presence of TNP-protein and activated macrophages that are not Ia+. This form of suppression is nonspecific at the effector stage; i.e., anti-TNP TsF inhibits a non-TNP binding cell line, TEPC 15, as long as TNP-protein and activated macrophages are present. Moreover, suppression occurs even when myeloma targets and AC are separated by cell-impermeable membranes. These results are consistent with the view that hapten-reactive TsF binds to antigen on the surface of macrophages and induces these cells to secrete nonspecific immunosuppressive molecules. Thus, different types of AC may play fundamentally different roles in TsF-mediated suppression; they may either bind and present TsF to targets (as in the case of idiotype-specific TsF) or secrete nonspecific immunosuppressants as a consequence of a TsF-antigen interaction (hapten-specific TsF). Autonomous, suppressible targets provide valuable experimental systems for analyzing the cellular interactions in T cell-mediated suppression.
Loss of proliferative capacity and T cell immune development potential by bone marrow from mice undergoing a graft-vs-host reaction.
Authors: Iwasaki T , Fujiwara H , Iwasaki T , Shearer G M 
Published: December 2022

Abstract
The inoculation of parental T lymphocytes into healthy, immune-competent F1 hybrid mice can result in severe immunologic abnormalities including immune deficiency in the recipients. To test whether stem cell function could also be affected in F1 mice undergoing a parental-induced graft-vs-host (GVH) reaction, T cell-depleted bone marrow from parentally injected F1 mice was tested for stem cell proliferative capacity and for differentiation into functional T cells by transplantation of bone marrow from GVH mice into lethally irradiated, syngeneic F1 test recipients. Stem cell proliferative capacity was assessed in the repopulating spleens of the test mice by the in vivo [125I]Iodo-2'-deoxyuridine assay. An eightfold to 10-fold reduction could be observed in the proliferative capacity of marrow from mice in which a GVH reaction had been induced 6 wk earlier. The GVH-induced hematopoietic defect required parental T cell recognition of both class I and class II H-2 alloantigens expressed by the F1 host. No suppressor cell activity was detected in the marrow of GVH mice. We did not detect a defect in the microenvironment of mice injected with parental marrow, but we did observe a severe and long-lasting defect in the ability of GVH F1 recipients to support the growth of F1 bone marrow. Spleen cells of test recipients repopulated with marrow from GVH donors exhibit in vitro defects in T and B lymphocyte functions. These findings indicate that the GVH reaction can affect early stages in the development of the hematopoietic system, both in terms of stem cell proliferative capacity and of long-term T lymphocyte functional potential.