bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell unresponsiveness to the mitogenic activity of OKT3 antibody results from a deficiency of monocyte Fc gamma receptors for murine IgG2a and inability to cross-link the T3-Ti complex.
Authors: Ceuppens J L , Bloemmen F J , Van Wauwe J P 
Published: December 2022

Abstract
We recently identified defective monocyte accessory function as the cause of T cell unresponsiveness to the mitogenic activity of OKT3 antibody in cultures of peripheral blood mononuclear cells (PBMC) from five healthy subjects, members of one family. We now report that the underlying abnormality in nonresponders is at the level of monocyte Fc gamma receptors for murine IgG2a. T cell unresponsiveness was not restricted to the signal provided by OKT3 but occurred also for two other anti-T3 antibodies of the IgG2a subclass, in contrast to a normal proliferative response to IgG1 anti-T3 antibodies in one of the OKT3 nonresponders. By using cytofluorography, we found that monocytes from responders but not from nonresponders bound OKT3-FITC to their membrane. The binding could be blocked by mouse IgG2a and by human IgG, but not by mouse IgG1 nor by serum albumin. The data suggest that, through specific Fc gamma receptors for murine IgG2a, monocytes bind the Fc portion of OKT3 during T cell activation. The function of this Fc gamma receptor binding was further studied by culturing PBMC from nonresponders on plates coated with affinity-purified goat anti-mouse IgG antibodies as a substitute for monocyte Fc gamma receptors. The addition of OKT3 to nonresponder PBMC, cultured on such plates, resulted in T cell activation, as evidenced by thymidine incorporation, IL 2 production, and expression of IL 2 receptors. Soluble anti-mouse IgG was not able to substitute for monocyte Fc gamma receptors. The results demonstrate the existence of polymorphism in monocyte Fc gamma receptors for murine IgG2a. They also substantiate that an essential helper function of monocytes in T cell activation by anti-T3 is to provide a matrix for multimeric binding of the Fc portion of the anti-T3 antibodies in order to cross-link T3 molecules.
Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo.
Authors: Beutler B A , Milsark I W , Cerami A 
Published: December 2022

Abstract
A highly specific radioreceptor assay for cachectin/tumor necrosis factor (TNF) was utilized to measure the time course of lipopolysaccharide (LPS)-induced hormone production in rabbits. Cachectin/TNF bioactivity was monitored in the same serum samples by measuring lipoprotein lipase (LPL) suppression in 3T3-L1 cells. Cachectin/TNF is produced in large quantities by LPS-treated rabbits without priming by bacillus Calmette Guérin, C. parvum, or other agents. Nanomolar concentrations of the hormone are achieved, with peak levels occurring at 2 hr postinjection; the hormone is rapidly cleared thereafter. In separate studies, mice were used to assess the distribution and metabolic fate of cachectin/TNF. Radioiodinated hormone is cleared from the plasma with a half-life of 6 to 7 min. Studies of the tissue distribution of label after injection demonstrate that liver, kidneys, skin, and gastrointestinal tract take up most of the hormone. Electrophoretic analysis of tissues recovered from injected animals suggests that the hormone is very rapidly degraded after binding.
Characterization of human IgG Fc receptors.
Authors: Vaughn M , Taylor M , Mohanakumar T 
Published: December 2022

Abstract
A murine monoclonal antibody, KuFc79, has been developed that reacts with human IgG Fc receptors on monocytes, B lymphocytes, and granulocytes. The specificity of KuFc79 for Fc receptors was demonstrated by the ability of Fab fragments to block Fc-mediated phagocytosis by monocytes. This finding was further substantiated by the decrease of KuFc79 binding to monocytes and granulocytes (58 and 70%, respectively) after modulation of surface IgG receptors with aggregated IgG. In addition, Fab KuFc79-conjugated Sepharose was used to isolate functional IgG Fc-binding molecules from soluble extracts of the human monocyte-like cell line U937. By immunoprecipitation, it was further shown that KuFc79 immunoprecipitated molecules of 42,000 and 70,000 daltons from U937 and a human lymphoblastoid cell line, SB. A lower m.w. species of approximately 33,000 was also precipitable from granulocytes. Extensive microheterogeneity of these molecules was noted by isoelectric focusing, which appears to be due to differential sialation.
A1 and A2 erythrocytes can be distinguished by reagents that do not detect structural differences between the two cell types.
Authors: Furukawa K , Mattes M J , Lloyd K O 
Published: December 2022

Abstract
The differential reactivity of four mouse monoclonal antibodies (AbCB, AbHT29-36, AbM2, and AbS12) and Dolichos biflorus lectin with A1 and A2 erythrocytes was analyzed. Only AbS12 and D. biflorus lectin were able to preferentially agglutinate A1 erythrocytes. AbS12 is known to react only with short chain, unbranched structures (such as Aa-2 and Ab-2 glycolipids) and not with longer chains or with type 3 and type 4 structures. D. biflorus was shown to have a similar specificity by lectin staining of glycolipids separated by thin-layer chromatography. Analysis of the binding of radiolabeled AbCB and AbS12 to A1 and A2 erythrocytes by Scatchard analysis showed that, whereas the former antibody recognizes high-affinity sites on both A1 and A2 cells, AbS12 reacts with high-affinity sites only on A1 cells. Because A1 and A2 erythrocytes have a similar complement of short chain type 2 glycolipids, although in different amounts, it is suggested that AbS12 and D. biflorus lectin differentiate between the two cell types on the basis of quantitative, nonstructural features. This is in contrast to AbTH1, which reacts with a repetitive A epitope (type 3 A chain) and distinguishes between A1 and A2 cells based on the preferential expression of type 3 A chains in A1 erythrocytes. Thus, two views of A1/A2, i.e., qualitative vs quantitative are correct, depending on the properties of the reagent being used to distinguish between the two cell types.
Influence of genetically inherited complement deficiencies on humoral immune response in guinea pigs.
Authors: Böttger E C , Hoffmann T , Hadding U , Bitter-Suermann D 
Published: December 2022

Abstract
To assess the role of complement in the induction of the humoral immune response, we studied the antibody response of guinea pigs genetically deficient in the second component of the classical complement pathway (C2D-GP) to bacteriophage phi X 174--a T cell-dependent antigen--in comparison with normal guinea pigs and C4D-GP, for which a disturbance in induction of antibody response has been described. We were able to establish a clear dose-response relationship: with low doses of antigen (1 X 10(9) PFU/kg), the antibody response of both complement-deficient strains was grossly impaired as compared with normal guinea pigs. After primary immunization, the peak antibody titer was diminished (1 log10) and declined rapidly; after secondary immunization, the diminution became even more distinct. Both complement-deficient strains had unusual secondary antibody responses almost identical to their primary ones, and amplification of antibody titer, as well as regular isotype switch from IgM to IgG, was absent. By increasing the antigen dose (2 X 10(9) PFU/kg), the antibody responses of the complement-deficient guinea pigs tend to normalize, and when high doses of antigen (1 X 10(10) PFU/kg) were used, the behavior of the complement-deficient animals was nearly indistinguishable from that of normal animals. Partial restoration of the immune response was seen when substituting the genetic complement deficiency by giving serum as source of the missing complement component. The important contribution of the C2 deficiency is given by the now compelling evidence that it is not the missing individual component itself, but rather the common block in sequential activation of C3 via the classical pathway in both complement deficiencies, that is responsible for the impaired humoral immune response, especially at low antigen doses. We therefore postulate that an intact classical pathway contributes to reaching a normal humoral immune response.
Test of a theory relating to the cross-linking of IgE antibody on the surface of human basophils.
Authors: MacGlashan D W , Dembo M , Goldstein B 
Published: December 2022

Abstract
Recent mathematical models of bivalent hapten-induced histamine release from basophils predict that under appropriate conditions histamine release is maximum when cross-link formation is maximum, at a hapten concentration equal to 1/(2Ka), where Ka is the average affinity constant of the hapten for a single IgE binding site. To test this prediction we sensitized human basophils with a monoclonal anti-dinitrophenol IgE and generated histamine release dose-response curves with a bivalent hapten, alpha, epsilon-DNP-lysine. The monoclonal IgE has a published affinity constant of 7.1 X 10(7) M-1 for epsilon-DNP-lysine as determined by equilibrium dialysis. From the position of the maximum of the histamine dose-response curves, both in the presence and in the absence of monovalent DNP hapten, we determine that the sensitizing IgE has an intrinsic affinity constant of 6.9 +/- 0.5 X 10(7) M-1 for epsilon-DNP-lysine and 1.2 +/- 0.6 X 10(6) M-1 for alpha-DNP-lysine. The agreement between the two estimates of the epsilon-DNP-lysine affinity constant, one from histamine release experiments involving surface bound IgE and one from binding experiments involving IgE free in solution, 1) is consistent with a central prediction of the theory of cross-linking and 2) indicates that the hapten-binding properties of the IgE are unaffected by its being bound to Fc epsilon receptors on the basophil surface.
De novo expression of T cell markers on Theileria parva-transformed lymphoblasts in cattle.
Authors: Naessens J , Newson J , Bensaid A , Teale A J , Magondu J G , Black S J 
Published: December 2022

Abstract
We describe monoclonal antibodies that detect two new membrane antigens on bovine T cells. One molecule is only expressed on activated T cells and has a m.w. of 100,000. The other antigen is a glycoprotein that is precipitated as two bands of m.w. 150,000 and 158,000 and is expressed on a subpopulation of T cells and all myeloid cells. We show that when bovine lymphocytes are transformed by the protozoan parasite Theileria parva, both antigens become expressed on the cell surface. The infected cell acquires the phenotype of a proliferating T cell, irrespective of its precursor cell phenotype.
The association of enhancing antibodies with seroconversion in humans receiving a dengue-2 live-virus vaccine.
Authors: Eckels K H , Kliks S C , Dubois D R , Wahl L M , Bancroft W H 
Published: December 2022

Abstract
A group of human subjects, some with yellow fever (YF) antibodies, volunteered for testing of a live-attenuated dengue-2 (DEN-2) vaccine. Serum samples taken before DEN-2 vaccination were tested for their ability to enhance infection of human monocytes by DEN-2 virus. A significantly greater proportion of enhancing antibodies (Eab) were found in YF-immune (YFI) individuals (50%) as compared to those with no evidence of flavivirus infection (9.5%). Geometric mean titers of neutralizing and hemagglutination inhibiting antibodies to DEN-2 virus in YFI subjects with Eab were fourfold to seven-fold higher than in the YFI subjects without Eab in prevaccine sera and 10- to 35-fold higher than in non-immune volunteers. Additionally, levels of Eab in prevaccine sera were directly related to antibody titers found in postvaccine sera. The presence of Eab in the serum of a human subject before DEN-2 vaccination was a good predictor of the immune response after vaccination, and may in part be responsible for the higher seroconversion rate in YF immunes (90%) as compared to nonimmunes (61%) receiving this vaccine. This is the first human study to demonstrate that circulating Eab in non-DEN-immune persons is associated with an augmented immune response to DEN virus infection. This finding supports the hypothesis that cross-reactive antibodies against one flavivirus enhance an infection with another closely related flavivirus.
An unusual clonotypic determinant on a cytotoxic T lymphocyte line is encoded by an immunoglobulin heavy chain variable region gene.
Authors: Ucker D S , Kurasawa Y , Tonegawa S 
Published: December 2022

Abstract
We have detected, in a CTL clone, an mRNA homologous to an immunoglobulin heavy chain variable region (VH) gene segment. A full-length copy of this mRNA was cloned and sequenced, revealing that it is the transcript of an authentic, unrearranged VH gene. The predicted protein product of this expressed VH gene is an approximately 12-kilodalton polypeptide, with secretory signal peptide leader and no membrane-anchoring sequences. Using immunologic reagents generated against a synthetic peptide representing the carboxyl terminus of the VH protein, we detect this protein as a clonotypic cell surface molecule. Strikingly, the anti-peptide reagents also exert effects on CTL function clonotypically. Immunoprecipitation experiments suggest that the VH protein may be associated noncovalently with the consensus, major histocompatibility complex-restricted, antigen-specific T cell receptor alpha- and beta-chains on the cell surface of this CTL. We detect weakly cross-reactive material similar to the VH protein in electrophoretic mobility in other CTL clones and suggest the possibility that small VH-like molecules may constitute a novel class of receptor components with variable determinants involved in the binding of nominal antigen and contributing to overall receptor diversity.
Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (RIL 2) can mediate the regression of both immunogenic and nonimmunogenic sarcomas and an adenocarcinoma.
Authors: Lafreniere R , Rosenberg S A 
Published: December 2022

Abstract
The incubation of normal murine splenocytes in recombinant interleukin 2 (RIL 2) gives rise to lymphokine-activated killer (LAK) cells that are specifically cytotoxic to fresh noncultured, autologous, syngeneic, and allogeneic primary and metastatic tumor cells, but are not toxic to normal cells. We have recently shown that the systemic injection of RIL 2 given alone or in conjunction with LAK cells can reduce the number of established pulmonary and hepatic micrometastases from a weakly immunogenic sarcoma in mice. In this report we have analyzed the response of hepatic metastases (HM) induced from both a nonimmunogenic sarcoma (MCA-102) and an adenocarcinoma (MCA-38). Treatment of mice bearing HM from the MCA-102 and MCA-38 tumors revealed that low doses of RIL 2 (5000 to 25,000 U t.i.d.) had little if any anti-tumor effect when given alone (mean percent reduction over control for the MCA-102 tumor: 14%, for the MCA-38 tumor: 10%, p, not significant). Doses of 100,000 U of RIL 2 affected a 38 and 53% reduction in the number of metastases over control for the MCA-102 and MCA-38 tumors, respectively (p less than 0.05). However, when LAK cells were added to the same doses of RIL 2, the corresponding mean percent reduction over control was 90% (p less than 0.005) and 61% (p less than 0.05) for MCA-102 and MCA-38, respectively, at RIL 2 doses of 5000 to 25,000 t.i.d. At doses of 100,000 U of RIL 2 administered with LAK cells, the corresponding percent reductions were 98 and 99%, respectively (p less than 0.005). Therapy with LAK cells plus RIL 2 can also prolong the survival of these mice. In addition, the intraportal administration of LAK cells is more effective than the i.v. administration of these cells. Thus, treatment of established HM from a nonimmunogenic sarcoma and an adenocarcinoma can be successfully mediated by the systemic infusion of LAK cells with RIL 2. These findings provide a rationale for clinical trials of infusion of LAK cells with RIL 2 in the therapy of HM in humans.
Effect of myeloma IgE injections on passive and active cutaneous anaphylaxis in rats.
Authors: Spiegelberg H L , Canning K M , Scheetz M , Koppel G , Chiller J M 
Published: December 2022

Abstract
The ability of injected rat IgE myeloma protein IR162 to inhibit passive and active cutaneous anaphylaxis in Lewis rats was investigated. IgE injected i.p. 24 hr before the sensitization with IgE anti-ovalbumin (OVA) completely inhibited both IgE- and IgG2a-induced passive cutaneous anaphylactic (PCA) reactions at a dose (2.5 mg/100 g body weight) that resulted in peak serum concentrations of 150 micrograms IgE IR162/ml. Peak IgE IR162 serum concentrations of 20 to 60 micrograms/ml inhibited the PCA reaction in approximately 50% of the rats. Intracutaneous injection of a mixture of myeloma IgE and anti-OVA IgE in a ratio of 100:1 or more also inhibited the PCA reaction. In contrast, the PCA reaction was not inhibited by seven daily doses of IgE beginning 24 hr after passive sensitization. Likewise, the cutaneous anaphylactic reaction elicited in rats 14 days after immunization with OVA and Bordetella pertussis was not prevented by daily injections of myeloma IgE despite a 1000- to 3000-fold excess of the myeloma IgE to anti-OVA IgE serum concentration. The data demonstrate that parenteral administration of myeloma IgE inhibits the PCA reaction only when given before passive sensitization and does not prevent cutaneous anaphylaxis in actively immunized rats. Because myeloma IgE failed to inhibit anaphylactic reactions in actively immunized rats, it is questionable whether administering human IgE-derived synthetic peptides or recombinant DNA-produced IgE fragments will be able to prevent allergic diseases by blocking the IgE Fc receptors on mast cells.
Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen.
Authors: Stanisz A M , Befus D , Bienenstock J 
Published: December 2022

Abstract
We examined the effect of vasoactive intestinal peptide, substance P, and somatostatin on concanavalin A (1 microgram/ml)-induced lymphocyte proliferation and immunoglobulin (IgA, IgM, and IgG) synthesis by cells from spleens, Peyer's patches, and mesenteric lymph nodes. These neuropeptides (10(-7) to 10(-12) M) modulated immune responses in a dose-dependent manner. For a comparative study, neuropeptides were used at 10(-8) M concentration. Both vasoactive intestinal peptide and somatostatin significantly decreased DNA synthesis (30 to 50%), whereas substance P increased synthesis (40%) in lymphocytes from all organs tested. IgA synthesis was significantly altered by all of the neuropeptides tested, whereas IgM synthesis was less affected and IgG synthesis was virtually unchanged. Somatostatin inhibited IgA (20 to 50%) and IgM (10 to 30%) synthesis in lymphocytes from all three organs. Substance P increased IgA synthesis in mesenteric lymph nodes (50%), spleens (70%), and Peyer's patches (300%). It also increased IgM synthesis in Peyer's patches (20%) and spleens (30%), but was without effect on IgM synthesis in mesenteric lymph nodes. Vasoactive intestinal peptide increased the IgA response in mesenteric lymph nodes (20%) and spleens (30%), but inhibited IgA synthesis in lymphocytes from Peyer's patches (60%). Interestingly, in Peyer's patches, IgM synthesis was increased by vasoactive intestinal peptide (80%), whereas it was unchanged in mesenteric lymph nodes and spleen. Thus, not only did these neuropeptides have different effects on the production of different immunoglobulin isotypes, but their effect was also organ-specific. Because neuropeptides which are abundant in the intestine can modulate IgA and other immunoglobulin synthesis in vitro, they may play a significant regulatory role in mucosal immune responses in vivo.
Phorbol-ester stimulated lysis of weak and nonspecific target cells by cytotoxic T lymphocytes.
Authors: Russell J H 
Published: December 2022

Abstract
We have investigated the effects of short-term incubation of cloned and in vivo-produced cytotoxic T lymphocytes (CTL) with phorbol esters on their lytic activity against weak and nonspecific targets. These experiments demonstrate that 4 beta-phorbol-12-myristate, 13-acetate (PMA), 4 beta-phorbol-12,13-dibutyrate, and 4 beta-phorbol-12,13-didecanoate, but not the 4 alpha-phorbol-12,13 didecanoate esters stimulate the lytic apparatus. The stimulation is specific for the CTL rather than the target and appears to be nearly instantaneous in action. This rapid stimulation of the CTL lytic process is consistent with previously reported effects of phorbol esters associated with T cell activation in other functional assays.
The pigeon cytochrome c-specific T cell response of low responder mice. I. Identification of antigenic determinants on fragment 1 to 65.
Authors: Suzuki G , Schwartz R H 
Published: December 2022

Abstract
An examination of the proliferative response to pigeon cytochrome c fragments 1 to 65 and 1 to 80 by T cells from mice that are low responders to the native molecule revealed that some of the strains could respond to antigenic determinants on these fragments. T cell clones derived from B10.A(3R) and B10.A(4R) mice were used to characterize the antigenic determinants on fragment 1 to 65. All of the clones recognized syngeneic A beta:A alpha Ia molecules as their restriction element. Three B10.A(3R) clones and six B10.A(4R) clones recognized fragment 39 to 65. Another four B10.A(4R) clones responded to fragment 1 to 38. By stimulating with a series of cytochrome c fragments from different species, as well as a synthetic peptide, it was possible to localize the antigenic determinant(s) recognized by the B10.A(3R) clones to residues 45 to 58. Each clone showed a unique pattern of responsiveness to the various fragments, suggesting a diversity of T cell receptors specific for the same peptide. One B10.A(3R) clone could be stimulated by many of the 1 to 65 fragments in association with allogeneic B10.SM presenting cells and by tuna fragment 1 to 65 in association with B10.M presenting cells, although the rank order of potency for several of the fragments was different than that observed with syngeneic antigen-presenting cells. In addition, the clone was poorly reactive to a synthetic peptide containing a conservative substitution, serine for threonine, at position 49. The implications of these results for subsite dissection (agretope and epitope) of the antigenic determinant recognized by this clone are discussed.