bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of deoxycoformycin in mice. II. Differences between the drug sensitivities and purine metabolizing enzymes of transplantable lymphomas of varying immunologic phenotypes.
Authors: Ratech H , Kim J , Asofsky R , Thorbecke G J , Hirschhorn R 
Published: December 2022

Abstract
Transplantable BALB/c and AKR lymphomas of different cell surface immunologic phenotypes have distinctive patterns of response to the ADA inhibitor DCF in vivo and in vitro. BAL 9, a lymphoma of the Lyt-1+,2+ T cell phenotype, was the most sensitive to DCF in vivo, and its DNA synthesis was inhibited more than 95% when cultured in the presence of dAr and DCF in vitro. This was correlated with a 10-fold increase in dATP content. The ADA and AMPDA activities were both high. Two lymphomas of the Lyt-1-,2+ T cell phenotype, BAL 5 and AKTB - lt , as well as two B cell phenotype lymphomas, A20 .3 and AKTB -lb, were all moderately inhibited in their in vivo growth if enough DCF was administered. However, their DNA synthesis in vitro was only inhibited 8 to 24% by dAr and DCF, there was only a twofold increase in the accumulation of dATP, and ADA and AMPDA activities were both low in the two BALB/c lymphomas tested. BAL 13, the only lymphoma of the Lyt-1+,2- phenotype examined, was completely resistant to DCF in vivo and in vitro. When cultured in the presence of dAr and DCF there was a transient increase in dATP content, followed by an abrupt decline. AMPDA activity was five to seven times greater than in the other lymphomas tested. ADA activity was moderate. The activities of 5' nucleotidase and of adenosine kinase were low and approximately equal in all the BALB/c lymphomas. These results suggest that the response to DCF by lymphomas of various immunologic phenotypes can be correlated with their nucleoside metabolism. The sensitivity of BAL 9 and the resistance of BAL 13 to DCF are correlated with their tendency to accumulate dATP and with their AMPDA and ADA activity ratios. The moderate sensitivity to DCF in vivo of the other T and B cell lymphomas, however, could not be clearly explained by any of the in vitro parameters thus far investigated, and this suggests that mechanisms inhibiting lymphoma proliferation other than dATP accumulation may be operating.
Characteristics of amplifier T cells involved in the antibody response to the capsular polysaccharide of type III Streptococcus pneumoniae.
Authors: Taylor C E , Stashak P W , Chiang J , Leiserson W M , Caldes G , Prescott B , Baker P J 
Published: December 2022

Abstract
Amplifier T cell activity can be transferred by spleen cells harvested 72 hr after priming with type III pneumococcal polysaccharide (SSS-III) and can be abolished by treating the transferred cells with monoclonal anti-Lyt-1, or anti-Thy-1 antibodies in the presence of complement; thus, amplifier cells represent a distinct subpopulation of T cells. Amplifier T cells were found to be sensitive to irradiation but not to treatment with cyclophosphamide. When amplifier cells were transferred to athymic nude (nu/nu) mice, the enhancement obtained was much greater than that produced in thymus-bearing (nu/+) mice; this is presumably due to the lack of suppressor T cell activity in nu/nu mice that enables amplifier T cell activity to be expressed more fully. Amplifier T cells also were found to be present in peripheral blood; these amplifier T cells were Lyt-2- in phenotype. Although the induction and activation of amplifier T cells appear to be antigen-specific, the product made by amplifier T cells may not be antigen specific in its mode of action. Because amplifier T cells can be induced and activated by exposure to immune B cells, specificity is presumably due in whole or in part to the ability of amplifier T cells to recognize the idiotypic determinants of B cell-associated antibody specific for SSS-III.
Stage-specific and common antigens of Brugia malayi identified with monoclonal antibodies.
Authors: Canlas M M , Piessens W F 
Published: December 2022

Abstract
To identify parasite antigens that trigger protective, pathogenic, and allergic immune responses during filarial infections, we generated a series of monoclonal antibodies to infective larvae, adult worms, and microfilariae of Brugia malayi, a human pathogen. Quantitative and qualitative analysis of the reaction patterns of these monoclonal antibodies indicates the existence of stage-specific antigens of B. malayi, as well as of antigens shared by different stages of this parasite and by other related and unrelated helminths. These antibodies should provide invaluable tools for the analysis of host-parasite interactions in filariasis at the molecular level.
Large granular lymphocytes provide an accessory function in the in vitro development of influenza A virus-specific cytotoxic T cells.
Authors: Burlington D B , Djeu J Y , Wells M A , Kiley S C , Quinnan G V 
Published: December 2022

Abstract
We report that large granular lymphocytes (LGL) have an accessory function in the development of cytotoxic T cells (Tc) through the production of soluble factor(s). LGL and T cells were separated on Percoll gradients and the ability of the separated and of the recombined LGL and T cells to generate influenza A virus-specific Tc activity was measured. When stimulated by virus-infected, irradiated, adherent cells, neither LGL nor T cells cultured separately produced Tc activity. When they were co-cultured, however, even if separated by a 0.22-micron pore size membrane, Tc responses were readily generated from the small T cell precursors and natural killer activity was maintained in the LGL. Thus, LGL were required as accessory cells for Tc responses to occur and the effect was mediated by a soluble factor(s). alpha-Interferon (IFN) was produced in cultures containing LGL and/or stimulating adherent cells, whereas gamma-IFN was only produced in cultures containing both LGL and T cells. Therefore, neither alpha- nor gamma-IFN appeared to be the LGL produced soluble factor that mediated the accessory effect of LGL on Tc responses.
Use of JH4 joining segment gene by an anti-arsonate antibody that bears the major A-strain cross-reactive idiotype but displays diminished antigen binding.
Authors: Slaughter C A , Jeske D J , Kuziel W A , Milner E C , Capra J D 
Published: December 2022

Abstract
One of the antibody families utilized by the A/J mouse in its response to p-azophenylarsonate (Ars) is characterized by the expression of the major anti-arsonate cross-reactive idiotype (CRI) of the A strain. This family has been termed the Ars-A family. A hybridoma antibody (HP 101F11 ) obtained after immunization of an A/J mouse with Ars was identified initially as displaying the CRI, but was subsequently found to bind antigen at a level much lower than most members of the Ars-A family. The results of binding studies suggested that HP 101F11 possesses reduced avidity for antigen. When isolated light and heavy chains were allowed to recombine with the heavy and light chains of a strongly antigen-binding, strongly CRI-positive antibody of the Ars-A family (HP 93G7 ), the low level of antigen binding by HP 101F11 was found to be due to a structurally variant heavy chain. Whereas antibodies of the Ars-A family with normal avidity for antigen had been shown to use the JH2 joining segment gene, amino acid sequence analysis of HP 101F11 revealed that this antibody has a JH segment with a sequence identical to that encoded by a portion of a different JH gene, JH4 . The implication that 101F11 uses the JH4 gene instead of JH2 was supported by the observation that the productively rearranged gene is associated with an Eco R1 restriction fragment 0.95 Kb smaller than the corresponding fragments of Ars-A hybridomas with normal avidity for antigen. The size difference of 0.95 Kb corresponds exactly to the known distance between the JH2 and JH4 genes in BALB/c germline DNA. In addition to the structural differences immediately attributable to the use of JH4 , HP 101F11 has shown an amino acid interchange in the DH segment, and a single amino acid deletion at the DH-JH boundary. These results show that variation among members of the Ars-A family in the DH and/or JH segments provides alternative structural forms of Ars-A antibodies upon which selective processes can operate during the course of an immune response.
Compared mechanisms of tumor cytolysis by human natural killer cells and activated polymorphonuclear leukocytes.
Authors: Abrams S I , Brahmi Z 
Published: December 2022

Abstract
The mechanism(s) of natural killer (NK) cell-mediated cytotoxicity (CMC) remains largely unknown. In this study, we investigated the possibility of human NK cells to exhibit an oxidative burst (OB) after stimulation by K562, an NK-sensitive target cell (TC). The addition of catalase (CAT) or superoxide dismutase (SOD) to the NK-mediated cytotoxic assay had no effect on NK-CMC. In contrast, CAT and SOD effectively modulated the cytotoxicity mediated by phorbol-12-myristate-13-acetate (PMA)-activated polymorphonuclear leukocytes (PMNL) against three different tumor TC, including K562. CAT abrogated, while SOD enhanced PMA-activated PMNL-mediated cytotoxicity. The synergistic effect of SOD and PMA was suppressed in a dose-dependent fashion by CAT. Furthermore, by chemiluminescence (CL) and SOD-inhibitable reduction of cytochrome c, we failed to detect an OB associated with K562-stimulated NK cells. PMNL, however, rapidly responded to PMA (10 ng/ml), generating almost 10(6) cpm within 20 min and 26.7 nM O-2/10(6) cells/30 min, as detected by CL and reduction of cytochrome c, respectively. Finally, K562 alone, at cell concentrations corresponding to effector cell:target cell (EC:TC) ratios of 1:1 and 1:10, reduced cytochrome c, but this reduction was not inhibited by SOD, thus suggesting a diaphorase activity. Overall, we show that: a) tumor cell destruction by human NK cells and by PMA-activated PMNL is mediated by different mechanisms; and b) NK-CMC against a sensitive TC does not involve an OB.
Inhibition of T cell responses to alloantigens and polyclonal mitogens by Ly-5 antisera.
Authors: Harp J A , Davis B S , Ewald S J 
Published: December 2022

Abstract
The effects of Ly-5 alloantisera on the generation of cytotoxic T cells (CTL), on the effector phase of CTL killing, and on polyclonal mitogenesis were studied. Ly-5 antisera added at the beginning of mixed lymphocyte culture (MLC) suppressed the production of CTL in an allele-specific manner. Neither Ly-5.1 nor Ly-5.2 antisera inhibited the generation of cytotoxic effectors by Ly-5.1/Ly-5.2 heterozygous spleen cells; however, a combination of Ly-5.1 and Ly-5.2 antisera markedly suppressed the appearance of Ly-5 heterozygous CTL. Similarly, Ly-5 antisera inhibited the effector phase of CTL killing in an allele-specific manner. In addition, Ly-5 alloantisera specifically blocked concanavalin A and oxidative mitogenesis of splenocytes carrying the appropriate Ly-5 alloantigen. The results are discussed in light of a possible functional role of Ly-5 molecules in immune processes.
A human alloreactive inducer T cell clone that selectively activates antigen-specific suppressor T cells.
Authors: Mohagheghpour N , Damle N K , Moonka D K , Terrell C P , Engleman E G 
Published: December 2022

Abstract
We showed previously that T cells with the phenotype Leu-3+,8+ are required for the induction of antigen-specific Leu-2+ suppressor cells. Furthermore, when mixed lymphocyte reactions are carried out in the presence of 1 microgram/ml cyclosporin A (CsA), such cultures lead preferentially to the activation of alloantigen-specific suppressor-inducer Leu-3+,8+ cells. In an attempt to generate a clone of T cells with such specific suppressor-inducer properties, we activated Leu-3+,8+ T cells with allogeneic (HLA-DR4+) lymphocytes in the presence of CsA. Clone SP-21, derived by propagating such activated T cells with conditioned medium containing IL 2, is a noncytotoxic, nonsuppressor clone that specifically proliferates to allogeneic cells bearing HLA-DR4 antigen. When cultured with fresh autologous Leu-2+ cells in the absence of HLA-DR4+ cells, clone SP-21 selectively activates Leu-2+ suppressor cells, which inhibit the response of fresh Leu-3+ cells to DR4+ stimulator cells. On the other hand, clone SP-21 fails to induce cytolytic T cells or to help B cell differentiation. These results demonstrate that a T cell clone with a remarkably narrow functional repertoire nonetheless contains and transmits all of the signals necessary for the activation of antigen-specific suppressor cells.
Suppressor T cell recognition of major and minor histocompatibility alloantigens: selected suppression of MHC-directed responses by minor alloantigen Ts.
Authors: Perry L L , Williams I F , Dirusso S 
Published: December 2022

Abstract
The induction of suppression by i.v. administered alloantigens in the murine host was analyzed as a model of the possible effects of blood transfusion on transplant survival. The results indicated that suppressor T cells (Ts) specific for minor histocompatibility alloantigens could be readily induced by the i.v. presentation of minor alloantigen-disparate spleen cells. In contrast, similar priming with cells differing solely at the H-2 major histocompatibility complex stimulated only positive T cell immunity, with no evidence of suppression. The induction of H-2 directed Ts activity could be accomplished only by i.v. priming with major plus minor incompatible donor cells, suggesting that suppressor cell recognition of minor alloantigens may have facilitated the generation of Ts against H-2-encoded major transplantation antigens. A role for minor histocompatibility antigens in the regulation of H-2-specific immunity at the effector level was also indicated. Ts induced by i.v. pretreatment with minor antigen-disparate donor cells not only suppressed the delayed-type hypersensitivity (DTH) response to the relevant minor alloantigens, but also inhibited DTH against unrelated H-2 alloantigens introduced during subsequent intradermal immunization. Suppression of H-2-directed T cell reactivity was specific in that the presence of the Ts-inducing minor alloantigens was also required and occurred only when the minor and unrelated major alloantigens were presented within the same inoculum, if not on the same cell surface. The capacity of Lyt-2+Ts or Ts-derived suppressive factors specific for one set of cell surface molecules to modulate responses to an unrelated group of surface antigens does not appear to represent a general phenomenon, because similar suppression of immunity to unrelated tumor-specific transplantation antigens by minor-specific Ts was not observed. These results are discussed with respect to the possible mechanism of H-2-directed suppression and the role of the I region in Ts recognition of antigen.
Characterization of monoclonal B cell growth factor (BCGF) produced by a human T-T hybridoma.
Authors: Butler J L , Ambrus J L , Fauci A S 
Published: December 2022

Abstract
We previously demonstrated the development of a cloned human T cell hybridoma that secretes B cell growth factor (BCGF) in the absence of demonstrable interleukin 2 or B cell differentiation factor. Sephadex gel filtration chromatography demonstrated the m.w. of this factor to be 18 to 20K. The present studies were performed to further characterize the biochemical properties of the molecule and to determine its target cell specificity. Temperature stability studies showed the monoclonal BCGF to be stable at 37 degrees C for 12 hr and at 70 degrees C for 15 min; however, most (93%) of the activity was lost after incubation at 70 degrees C for 30 min. Aliquots of hybridoma supernatant were exposed to buffer solutions with variable pH with no diminution in activity over a pH range of 4.0 to 10.0 BCGF activity was not affected by 2-mercaptoethanol, neuraminidase, or nucleic acid denaturing enzymes. In contrast, all activity was destroyed by 10 M urea, trypsin, and chymotrypsin. Chromatofocusing demonstrated the isoelectric point of BCGF to be 6.3 to 6.6. Finally, absorption experiments demonstrated that BCGF activity was absorbed by large, activated B cells. Mitogen-stimulated T cell blasts, small resting B cells, and CESS cells failed to absorb BCGF activity from the hybridoma supernatant. These and future studies with purified monoclonal human BCGF should enhance our understanding of its immunochemical properties and of its role in the immunoregulation of human B cell responses.
HLA-DR antigens of autologous melanoma and B lymphoblastoid cell lines: differences in glycosylation but not protein structure.
Authors: Alexander S , Hubbard S C , Strominger J L 
Published: December 2022

Abstract
The HLA-DR antigen expressed on the surface of the human melanoma cell line SK-MEL-37 was characterized and compared with the HLA-DR antigen from the MU B lymphoblastoid cell line originating from the same individual. The HLA-DR heavy chain from SK-MEL-37 cells had an apparent mobility on SDS-PAGE slightly slower than that isolated from MU cells. In contrast, the HLA-DR light chains and the HLA-A,-B heavy chains from the two cell lines had identical mobilities. Double-labeled tryptic peptide mapping and limited N-terminal sequencing showed that the SK-MEL-37 HLA-DR antigen, like all previously examined B lymphoblastoid cell HLA-DR antigens, was homologous to the murine I-E/C subregion antigens and that the mobility difference of the SK-MEL-37 HLA-DR heavy chain was not attributable to differences in the primary structure of the polypeptide. Treatment of the cells with tunicamycin abolished the m.w. difference, suggesting that it was due to a change in glycosylation in SK-MEL-37. This was confirmed by analysis of the glycopeptides from pronase-digested HLA-DR light and heavy chains and HLA-A,B heavy chains purified from the two cell types. The results suggest 1) there is a difference in asparagine-linked oligosaccharide processing in the two cell types, with more of the larger complex glycans synthesized in the melanoma cells than in the B lymphoblastoid cells, 2) the effect is more pronounced with HLA-DR heavy chains than with HLA-DR light chains or HLA-A,B heavy chains, and 3) the oligosaccharide size difference is not solely due to sialic acid content.
Preparation and characterization of monoclonal antibodies reactive with porcine PBL.
Authors: Pescovitz M D , Lunney J K , Sachs D H 
Published: December 2022

Abstract
Partially inbred miniature swine have been developed in this laboratory as a large animal model for immunologic studies. For many of these studies, a source of large quantities of well standardized antibodies to lymphocyte cell surface markers would be extremely helpful. Screening of a large panel of murine anti-human monoclonal antibodies (MAb) for anti-pig cross-reactions was nonproductive. We have therefore prepared a panel of MAb from mice immunized with pig thymocytes. Twenty-six stable MAb were produced that reacted with Ficoll/Hypaque-purified porcine lymphocytes. Reactivity was detected by complement-mediated cytotoxicity and/or cell surface binding ELISA. FMF analysis was performed on unseparated, glass-adherent, nylon wool-adherent, or nylon wool-nonadherent PBL and on cell preparations from lymphoid organs. In addition, the m.w. of the antigens detected by certain of these MAb were determined by immunoprecipitation of extracts of 125I surface-labeled cells. The majority of the MAb were not subpopulation specific. Included in these were 74-11-10 (IgG2b), which was specific for a polymorphic class I MHC determinant, and 76-3-2 (IgG1), which reacted with either a monomorphic class I MHC determinant or beta 2-microglobulin. Another MAb, 74-9-3 (IgM), precipitated a high m.w. complex of three polypeptide chains that appeared similar to that of the common leukocyte antigen. Of special interest were six MAb that were specific for various subpopulations of PBL: 76-7-4 (IgG2a) reacts with peripheral B cells, and 60% of thymocytes but not peripheral T cells, a pattern consistent with the murine ThB antigen; 74-22-15 (IgG1) and 76-5-28 (IgM) react with macrophages and granulocytes; 76-6-7 (IgM) reacts with T cells, macrophages, and granulocytes but not B cells, a combination of reactivities not previously reported in other species; 74-12-4 (IgG2b) and 76-2-11 (IgG2a) react specifically with T cells. 74-12-4 precipitated an antigen of 55,000 m.w., and 76-2-11 precipitated an antigen of 35,000 m.w. The m.w. and tissue distributions suggest that 74-12-4 recognizes porcine T helper cells, whereas 76-2-11 recognizes cytotoxic and/or suppressor T cells.
Organelle-depleted human neutrophil cytoplasts used to study fmet-leu-phe receptor modulation and cell function.
Authors: Gallin J I , Metcalf J A , Roos D , Seligmann B , Friedman M M 
Published: December 2022

Abstract
Organelle-depleted human neutrophil cytoplasts were used to study N-formylmethionylleucylphenylalanine (fmet-leu-phe) receptor regulation and adaptation, aggregation, chemotaxis, and chemoattractant-elicited changes in shape, volume, and surface charge. Cytoplasts aggregated in response to the chemoattractant fmet-leu-phe, but the magnitude of the response was less than that in neutrophils. Unlike neutrophils, cytoplasts did not exhibit a second wave of aggregation with the addition of cytochalasin B and also failed to disaggregate. In chemotactic assays, cytoplasts migrated poorly into cellulose nitrate filters, and compared with intact neutrophils required a 100-fold greater concentration of fmet-leu-phe to elicit shape change. In contrast to neutrophils, cytoplasts did not decrease their surface charge in response to fmet-leu-phe and did not exhibit an increase in the binding of fmet-leu-[3H]phe after stimulation with phorbol myristate acetate. However, receptor adaptation and induced changes in membrane potential, as measured by using the membrane probe di-O-C5(3), were similar in cytoplasts and in neutrophils. The data suggest that the presence of functional intracellular organelles is required for normal aggregation and disaggregation, chemotaxis, and shape change induced by fmet-leu-phe, and also peptide receptor upregulation in response to secretagogues. The data show that peptide receptor adaptation occurs in the absence of secretory granules and is independent of receptor upregulation .
Control of mouse hepatitis virus replication in macrophages by a recessive gene on chromosome 7.
Authors: Smith M S , Click R E , Plagemann P G 
Published: December 2022

Abstract
We have identified and mapped a new locus that imparts resistance to productive infection of mouse hepatitis virus MHV(A59) in cultured macrophages. This locus maps 41.5 centimorgans from the albino locus on chromosome 7.
Monoclonal antibodies to DNA and RNA from NZB/NZW F1 mice: antigenic specificities and NH2 terminal amino acid sequences.
Authors: Eilat D , Hochberg M , Pumphrey J , Rudikoff S 
Published: December 2022

Abstract
Two anti-DNA hybridoma autoantibodies ( A52 , D42 ) were prepared by fusing spleen cells from unimmunized NZB/NZW F1 female mice with BALB/c myeloma cells. The monoclonal antibodies were purified to homogeneity and were analyzed for their antigen-binding specificities. The two anti-DNA antibodies bound single-stranded, double-stranded, and supercoiled DNA, with a marked preference for the single-stranded conformation. Competition experiments performed with synthetic polynucleotides, as well as chain reconstitution experiments, indicated that both the sugar-phosphate backbone and the heterocyclic bases of the nucleic acid are essential for antibody recognition. Amino terminal sequence analysis of A52 and two RNA-binding hybridoma proteins revealed that the heavy chains from all three were members of the VHII subgroup and that the A52 light chain was homologous to the VK8 subgroup. The D42 heavy chain was found to be similar to a phosphocholine-binding hybridoma of the VHIII subgroup.