bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of ecto-5' nucleotidase activity by functionally and phenotypically distinct subpopulations of human Leu-2+/T8+ lymphocytes.
Authors: Dianzani U , Massaia M , Pileri A , Grossi C E , Clement L T 
Published: December 2022

Abstract
Subsets of Leu-2+/T8+ cytotoxic/suppressor T lymphocytes were isolated by using various methods of purification and were investigated for expression of ecto-5' nucleotidase (5'NT) enzyme activity by radiochemical, cytochemical, and ultrastructural techniques. By using both the radiochemical and the cytochemical methods. T4-OKM1- cells displayed higher 5'NT activity in comparison with the entire T4- subpopulation. Analyses of the subpopulations of T4- (and predominantly Leu-2+) cells defined by the Leu-15 or Lyt-1 (9.3) monoclonal antibodies demonstrated that T4-Leu-15- and T4-Lyt-1+ cells displayed high 5'NT activity, whereas virtually no activity was present in T4-Leu-15+ and T4-Lyt-1-cells. At the ultrastructural level, the 5'NT reaction product was detected on the plasma membrane of a proportion of nongranular Leu-2+/T8+ lymphocytes, but no activity was found on cells with a granular lymphocyte (GL) morphology. 5'NT activity was also analyzed in peripheral blood mononuclear cells from one patient with expanded numbers of GL and two patients with GL leukemia. The enzymatic activity was significantly lower in these patients than in normal controls. This study provides new cytochemical evidence demonstrating the heterogeneity of Leu-2+/T8+ cells, and indicates that the population with the suppressor phenotype and function (Leu-15+/Lyt-1-, GL morphology) displays low or absent 5'NT activity, whereas the population composed of cytotoxic cell precursors (Leu-15-/Lyt-1+, nongranular morphology) has high 5'NT activity. Implications of these data for the interpretation of low 5'NT activity described in several immunodeficiency states and lymphoproliferative disorders are discussed.
Destruction of autologous human lymphocytes by interleukin 2-activated cytotoxic cells.
Authors: Sondel P M , Hank J A , Kohler P C , Chen B P , Minkoff D Z , Molenda J A 
Published: December 2022

Abstract
Human and murine lymphocyte populations differentiate into lymphokine activated killer (LAK) cells after in vitro or in vivo exposure to interleukin 2 (IL 2). LAK cells mediate destruction of neoplastic tissue in vitro and have been reported to spare normal tissue. However, systemic toxicity is observed in mice and patients receiving IL 2 infusions. Some aspects of this toxicity are similar to that seen in graft-vs-host disease, suggesting that IL 2 may cause an immune-mediated destruction of normal tissues. We have evaluated this issue by examining the destructive potential of fresh human lymphocytes cultured in media containing highly purified recombinant human IL 2. In the absence of any exogenous antigen or allogeneic stimulating cells, strong proliferative responses were induced after 6 days of exposure to IL 2. Lymphocytes harvested from these 6-day cultures were highly cytotoxic to K562 and Daudi target cells. These IL 2-activated cells were also cytotoxic against autologous and allogeneic normal lymphocyte target cells. This autologous lymphocyte destruction was detected in media containing autologous serum and was directly dependent on the concentration of IL 2 added to the cultures. These studies demonstrate that populations of IL 2-activated lymphocytes, containing LAK activity, can mediate low-level but significant destruction of normal lymphocytes in vitro.
Effect of interleukin 1 on the expression of interleukin 2 receptor (Tac antigen) on human natural killer cells and natural killer-like cell line (YT cells).
Authors: Shirakawa F , Tanaka Y , Eto S , Suzuki H , Yodoi J , Yamashita U 
Published: December 2022

Abstract
The effect of interleukin 1 (IL 1) on the expression of interleukin 2 receptor (IL 2R/Tac antigen) on human natural killer (NK) cells and the NK-like cell line, YT was studied with the use of a fluoresceinated anti-IL 2R monoclonal antibody and a Spectrum III flow cytofluorometer. IL 2R was expressed on approximately 10% of NK cells. The expression of IL 2R on NK cells was increased to approximately 25% by the in vitro culture with monocytes or IL 1 and to a less extent by the culture with IL 2 or interferon-gamma (IFN-gamma). IL 2R was expressed on approximately 50% of YT cells without any stimulations. The expression of IL 2R on YT cells was increased up to almost 100% by the culture with IL 1 or monocytes, but not with IL 2, IFN-alpha, IFN-beta, IFN-gamma, or lectins such as concanavalin A and phytohemagglutinin-P. IL 1 absorbed with YT cells or murine thymocytes lost both IL 1 activity detected by the stimulation of murine thymocyte proliferative response and enhancing activity of IL 2R expression on YT cells, suggesting that IL 1 has both activities. However, the assay system of the expression of IL 2R on YT cells is much more sensitive than the stimulation of murine thymocyte proliferative response. By the kinetic study, the enhancement of IL 2R expression was induced by only a 2-hr incubation of YT cells with IL 1. This enhancement did not proceed at 4 degrees C or by the treatment of YT cells with actinomycin D or cycloheximide, suggesting that this enhancement is energy dependent and requires the synthesis of RNA and protein but not DNA. Thus IL 1 plays an important role for the regulation of the expression of IL 2R on NK cells, and IL 1-dependent IL 2R expression on YT cells may give us a good model for the study of the molecular mechanism of the regulation of IL 2R expression.
C1s-induced vascular permeability in C2-deficient guinea pigs.
Authors: Strang C J , Auerbach H S , Rosen F S 
Published: December 2022

Abstract
Normal guinea pigs that have been intradermally injected with C1s exhibit increased vascular permeability at the injection site. Guinea pigs that are genetically deficient in complement component C2 do not exhibit increased vascular permeability when given a similar injection. The C2-deficient guinea pigs respond normally to injections of bradykinin and kallikrein, suggesting that these animals can respond to kinins and have a normal kininogen pathway. When the C2-deficient guinea pigs are given guinea pig C2 before C1s injection, increased vascular permeability is observed. These results demonstrate a definite requirement for complement component C2 in the generation of C1s-induced vascular permeability.
Analysis of neoplasms induced by Cas-Br-M MuLV tumor extracts.
Authors: Holmes K L , Langdon W Y , Fredrickson T N , Coffman R L , Hoffman P M , Hartley J W , Morse H C 
Published: December 2022

Abstract
Cas-Br-M is an ecotropic murine leukemia virus isolated from wild mice that induces a wide spectrum of hematopoietic neoplasms, including T and B cell lymphomas, myelogenous leukemias, and erythroleukemias. The purpose of this study was to determine if the induction of neoplasms belonging to multiple lineages was due to the ecotropic virus itself or to the generation of cell lineage-specific recombinant viruses. The results demonstrate that in some instances (two of 12 tumor extracts tested), recombinant viruses can be recovered from primary Cas-Br-M-induced tumors that will induce lymphomas of single lineages in mice inoculated as newborns. One of these viruses is a recombinant mink cell focus-forming virus that induces T cell lymphomas, and the other is a replication-defective, fibroblast-transforming virus that induces early B lineage lymphomas in mice. Histologic and flow microfluorometric cell surface antigen analyses of primary and in vitro adapted tumors are presented in support of a modified scheme of hematopoietic cell development.
Do sugar residues contribute to the antigenic determinants responsible for protection and/or abolition of protection in Leishmania-infected BALB/c mice?
Authors: Gorczynski R M 
Published: December 2022

Abstract
Intravenous inoculation of irradiated virulent promastigotes of Leishmania mexicana, or intradermal inoculation of avirulent temperature-sensitive clones of the same parasite, can protect BALB/c mice from progressive disease when challenged with parental organisms. However, if animals are prechallenged s.c. with irradiated parental parasites before (or shortly after, i.e., within 10 days) any other immunization regime is used, the s.c. challenge effectively suppresses development of protective immunity. The role of N-linked sugars on promastigotes in providing the determinants responsible for protection and/or suppression of protection in these assays has been examined. Growth of parasite in 2 micrograms/ml tunicamycin has no effect on incorporation of [3H]leucine but decreases incorporation of [3H]mannose by some 40 to 50%. Such tunicamycin-treated avirulent clones or irradiated virulent organisms are now unable to induce a protective response. However, tunicamycin-treated parental parasites given s.c. could still suppress the protection seen when irradiated parasites were given i.v. as immunogen. Tunicamycin-treated avirulent organisms given s.c. subcutaneously unlike the untreated avirulent clones, now also caused suppression of protection. These data suggest that the determinants responsible for development of protective immunity to L. mexicana in BALB/c mice are dependent on N-linked glycoproteins for their expression, unlike the determinants responsible for suppression of that protection. By using swainsonine as an alternative inhibitor of N-linked glycoprotein synthesis, the data additionally suggest that no complex processing of N-linked sugars takes place to reveal the immunogenic determinants in this system.
B lymphocytes are required for the generation of T cells that mediate healing of cutaneous leishmaniasis.
Authors: Scott P , Natovitz P , Sher A 
Published: December 2022

Abstract
The role that B lymphocytes and/or antibodies play in the healing of Leishmania major infections in genetically resistant C3H/HeN mice was investigated by monitoring the course of infection in animals that had been B cell depleted by treatment from birth with anti-IgM sera (mu-suppressed). L. major infection of mu-suppressed C3H/HeN mice produced lesions that were significantly larger than those induced in control animals, and failed to heal. Moreover, vaccinated mu-suppressed mice also developed chronic nonhealing infections, although their lesions were initially smaller than those developed by nonvaccinated mu-suppressed controls. The enhanced susceptibility of mu-suppressed mice could be completely overcome by adoptive transfer of T lymphocytes from mice that had spontaneously healed their lesions, and to a lesser extent by T lymphocytes from normal animals. Anti-leishmanial antibody responses were completely absent in mu-suppressed mice, regardless of whether they were lymphocyte reconstituted, whereas delayed type hypersensitivity (DTH) to leishmanial antigens was present in normal and mu-suppressed animals. The ability of immune T cells to protect mu-suppressed mice without restoring humoral responsiveness clearly indicates that antibodies are not necessary for healing leishmanial infections. Instead, the observed effect of mu-suppression argues that B lymphocytes are required for the generation of an effector T cell population, apparently unrelated to DTH, which mediates the healing of cutaneous lesions. These results thus provide the first evidence for the B cell and/or Ig dependency of a T cell population that is critical for the development of immunity against a microbial agent.
The murine gamma-chain of the T cell receptor is closely linked to a spermatocyte specific histone gene and the beige coat color locus on chromosome 13.
Authors: Owen F L , Taylor B A , Zweidler A , Seidman J G 
Published: December 2022

Abstract
With the use of standard genetic techniques, we have mapped the T cell gamma-chain gene locus (Tcrg) to the proximal end of mouse chromosome 13. Close genetic linkage was demonstrated between a restriction fragment length polymorphism in the Tcrg locus and a locus (HlS) encoding a spermatocyte-specific histone electrophoretic variant (HlS) by using recombinant inbred strains. Because HlS is closely linked to the dominant visible marker extra toes (Xt), Tcrg must be within 5 cM of the beige (bg) locus. Mice homozygous for the recessive mutation beige (bg/bg) show diminished pigmentation, enlarged lysosomes in granulocytes, and a selective deficiency of natural killer cell function. The bg mutation in mice is an animal model for humans with Chediak-Higashi syndrome; we speculate that the human gamma-chain may be closely linked to the human mutation and may be a useful diagnostic tool. Seven restriction enzymes identify five haplotypes of the highly polymorphic gamma-chain in mice.
A genetically engineered murine/human chimeric antibody retains specificity for human tumor-associated antigen.
Authors: Sahagan B G , Dorai H , Saltzgaber-Muller J , Toneguzzo F , Guindon C A , Lilly S P , McDonald K W , Morrissey D V , Stone B A , Davis G L 
Published: December 2022

Abstract
Chimeric immunoglobulin genes were constructed by fusing murine variable region exons to human constant region exons. The ultimate goal was to produce an antibody capable of escaping surveillance by the human immune system while retaining the tumor specificity of a murine monoclonal. The murine variable regions were isolated from the functionally expressed kappa and gamma 1 immunoglobulin genes of the murine hybridoma cell line B6.2, the secreted monoclonal antibody of which reacts with a surface antigen from human breast, lung, and colon carcinomas. The kappa and gamma 1 chain fusion genes were co-introduced into non-antibody producing murine myeloma cells by electroporation. Transfectants that produced murine/human chimeric antibody were obtained at high frequency as indicated by immunoblots probed with an antisera specific for human immunoglobulin. Enzyme-linked immunoabsorbent assay analysis demonstrated that this chimeric antibody was secreted from the myeloma cells and retained the ability to bind selectively to membrane prepared from human tumor cells. The chimeric immunoglobulin was also shown by indirect fluorescence microscopy to bind to intact human carcinoma cells with specificity expected of B6.2. The ability of chimeric antibody to recognize human tumor-associated antigen makes feasible a novel approach to cancer immunotherapy.
Influence of immunoglobulin-dependent T cells on antibody class switching.
Authors: Teale J M , Janeway C A 
Published: December 2022

Abstract
Normal and B cell-deficient, carrier-primed mice were irradiated and were adoptively transferred with B cells to evaluate the role of putative Ig- and B cell-dependent T cells in anti-hapten antibody responses. The response was analyzed by using the splenic focus assay, which allowed us to examine the frequency of responding B cells and the production of multiple isotypes by single precursor B cells. This analysis revealed that both primary and secondary B cells were activated at higher frequency in the spleens of normal recipients, and production of isotypes other than IgM and IgG1 was enhanced in normal recipients as compared with anti-mu-treated recipients. Both changes could be restored to control levels by co-transfer of T cells from normal donors primed with an unrelated carrier, provided the free carrier was added to the assay culture. These results are consistent with a role for Ig or B cell-dependent helper T cells in the optimal activation and the resulting isotype expression of both primary and secondary B cells.
The role of the accessory cell in mitogen-stimulated human T cell gene expression.
Authors: Kern J A , Reed J C , Daniele R P , Nowell P C 
Published: December 2022

Abstract
The role of the accessory cell in optimizing T cell proliferative responses to mitogens is a well known but poorly understood phenomenon. To further dissect the function of the accessory cell in allowing T cell proliferation, we compared mitogen-induced c-myc, interleukin 2 (IL 2), and IL 2 receptor gene expression in peripheral blood mononuclear cells (PBMC) and in T cells rigorously depleted of accessory cells through differential adherence and anti-Dr (anti-class II major histocompatibility antigen) monoclonal antibody complement-directed cytotoxicity. In cultures stimulated with phytohemagglutinin (PHA), a mitogen that requires accessory cells to induce T cell proliferation, expression of all measured genes was accessory cell dependent, since accumulation of their mRNA in PBMC was greater than that in cultures depleted of accessory cells. These genes varied in their accessory cell dependence, with IL 2 expression most dependent, c-myc expression least dependent, and IL 2 receptor expression intermediate in dependency. Use of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or ionomycin, mitogens that stimulate T cell proliferation independent of accessory cells, induced equal levels of gene expression in PBMC and in T cells depleted of accessory cells. These results suggest that PHA-stimulated T cells are dependent on an accessory cell signal(s) for optimal expression of the genes for c-myc, IL 2, and IL 2 receptor, and for proliferation. In addition, this signal(s) appears to be delivered early in the course of T cell activation events, since it can be bypassed by mitogens that directly activate protein kinase C (TPA) or induce calcium translocation (ionomycin). In addition, these data provide further evidence that expression of the c-myc protooncogene is insufficient for T cell mitogenesis, since PHA-induced accumulation of c-myc mRNA was only partially accessory cell dependent, whereas proliferation was completely accessory-cell dependent.
Role of self carriers in the immune response and tolerance. X. A lymphoid dendritic-like tumor, P388AD.2, acts as a novel immunogenic carrier for hapten.
Authors: Cogswell J P , Phipps R P , Scott D W 
Published: December 2022

Abstract
Hapten-modified spleen cells, peritoneal exudate cells, and certain lymphoid tumors preferentially induce specific tolerance after i.v. administration. In contrast to these tolerogenic carrier cells, we found that a haptenated lymphoid dendritic-like tumor, P388AD.2, acts as a potent immunogen after i.v. injection. The immunogenicity of P388AD.2 was analyzed by measuring the specific augmentation of plaque-forming cell (PFC) responses when spleen cells from mice previously injected with haptenated tumor cells were challenged in vitro with thymus-independent antigens. Optimal immunization was found to be dependent on cell dose and hapten concentrations. Further studies indicated that P388AD.2 elicited a response which was T cell-dependent and which involved both the so-called Lyb-3,5,7- and Lyb-3,5,7+ B cell populations. Injection of haptenated tumor into different mouse strains suggested that H-2 compatibility was required to prime B cells in vivo, although significant augmentation could also be achieved in allogeneic C57B1/6J mice. The enhanced PFC responses elicited in H-2b mice could not be explained by allo-recognition of class I or II MHC determinants. In toto, these results suggest that P388AD.2 acts as a unique accessory cell for the presentation of hapten-modified self.
Immunodeficiency of aging: restorative effects of phorbol ester combined with calcium ionophore.
Authors: Miller R A 
Published: December 2022

Abstract
Current models for lectin-induced T cell proliferation suggest that activation of protein kinase C (PK-C) and elevation of cytoplasmic Ca2+ may both play important roles in the earliest phases of signal transduction. To learn more about the relative inability of T cells from old mice to proliferate in response to mitogenic stimuli, we attempted to stimulate T cells by the synergistic effects of a PK-C activator, phorbol myristate acetate (PMA), and the calcium ionophore ionomycin. T cells from young mice respond as well to optimal combinations of these agents as they do to the strong polyclonal activator Con A, but T cells from old mice respond much better to PMA plus ionomycin than they do to Con A. This result suggests that an inability to transduce the signal supplied by extracellular ligands into the intracellular signals represented by Ca2+ and PK-C activators may underlie the age-associated loss of T cell reactivity. We also found evidence for a second defect in old T cells related to their response to elevated intracellular Ca2+: old T cells, compared with young, required higher levels of ionomycin for maximal proliferation.
Alloantigen-specific suppressor T cells are not inhibited by cyclosporin A, but do require IL 2 for activation.
Authors: Bucy R P 
Published: December 2022

Abstract
Alloantigen-specific suppressor T cells are activated from normal murine spleen cells in mixed lymphocyte reactions (MLR). These T cells are radioresistant and suppress the activation of cytotoxic T lymphocytes (CTL) in second primary MLR cultures. This report demonstrates that cyclosporin A (CsA) blocks the activation of these suppressor cells at a dose of 1 microgram/ml. However, reconstitution of CsA blocked cultures with IL 2 restores the activation of the suppressor T cells, but fails to significantly restore the activation of CTL in these same cultures. This differential activation requirement was used to establish T cell lines that demonstrate enriched suppressor cell activity but depletion of CTL activity. These findings are discussed in terms of the mechanism of action of CsA in these distinct T cell subsets and the relevance to models of allograft unresponsiveness.
Slower processing, weaker beta 2-M association, and lower surface expression of H-2Ld are influenced by its amino terminus.
Authors: Beck J C , Hansen T H , Cullen S E , Lee D R 
Published: December 2022

Abstract
To determine why Ld antigens are expressed on the cell surface at levels three to four times lower than Dd or Kd antigens, pulse-chase experiments were used to compare their rates of biosynthesis and processing. Electrophoresis on sodium dodecyl sulfate gradient polyacrylamide gels resolved immunoprecipitates of each of these histocompatibility complex class I molecules into a slower and faster species. During the chase period, the faster migrating species appeared to be converted to the slower migrating species in a time-dependent manner. However, the conversion of Ld from the faster to the slower migrating species proceeded significantly more slowly than did the conversion of either Dd or Kd. Endoglycosidase H sensitivity and cell surface radiolabeling were used to determine the glycosylation state and cell location of each species of Ld and Dd. The results from these experiments, along with the pulse-chase studies and cytofluorometric analyses, suggest that Ld possesses a much slower rate of processing from a faster migrating, high mannose-bearing species to a slower migrating, complex oligosaccharide-bearing species found on the cell surface. Analysis of the beta 2-microglobulin (beta 2-m) association confirmed that Ld is associated with less beta 2-m than Dd. To localize the structures on class I molecules influencing their surface expression, rate of processing, and beta 2-m association, the Ddm1 molecule was analyzed. The Ddm1 molecule of the mutant B10.D2-H-2dm1 has previously been shown to be a chimeric Dd (amino-terminal)/Ld (carboxyl-terminal) polypeptide. The surface expression, processing and beta 2-m association of Ddm1 were found to be similar to Dd rather than Ld, suggesting that each of these phenomena are influenced by protein structure in the amino terminus.