bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary chemical and biologic characterization of (Fc)TRF: an Fc fragment-induced T cell-replacing factor.
Authors: Thoman M L , Weigle W O
Published: December 2022

Fc fragment stimulation of Lyt-1+2- T lymphocytes triggers release of a T cell-replacing factor, here called (Fc)TRF. Chemical and biologic characterization of (Fc)TRF has been undertaken to provide information for its comparison with other T cell factors. Preliminary chemical characterization by column chromatography and isoelectric focusing suggest (Fc)TRF activity resides in a class of acidic molecules that fall into two size classes of 58-60,000 daltons and 35-40,000 daltons. This factor is distinct from Interleukin 2 (IL 2) as it has no T cell growth-promoting or costimulator activity, although it can also be generated by Con A activation of murine spleen cells. By these results (Fc)TRF has been defined as a unique T cell-replacing activity that promotes differentiation of B lymphocytes to antibody-secreting cells.
Immortalization of antigen specific, helper T cell lines by transformation with the radiation leukemia virus (RadLV).
Authors: Yefenof E , Azar Y , Eidelsztein P , Ben-Sasson S Z
Published: December 2022

Antigen-specific immune T lymphocytes of male C57BL/6 mice were enriched in vitro on monolayers of antigen-pulsed syngeneic macrophages. The cells were treated in vitro with RadLV and inoculated intrathymically into irradiated female C56BL/6 animals. Thymomas arising in the inoculated recipients were characterized as donor- (male) type according to their karyotype. In vivo and in vitro cell lines were established from the primary lymphomas, two of which (designated ROT/6.1 and ROT/6.2) were capable of providing antigen- (carrier) specific help in normal or preimmunized mice. None of the lymphomas could induce antigen-specific DTH reaction. Five months after their establishment, ROT/6.2 alone retained its carrier specificity. ROT/6.2 consisted mainly of Lyt-1+ cells, whereas the ROT/6.1 population was more heterogeneous and contained Lyt-1+, Lyt-2+, and Lyt-3+ cells. The carrier specificity of the latter may have been lost due to selection against the specific helper cells during prolonged passages.
Suppression of acute experimental allergic encephalomyelitis in guinea pigs by prior transfer of suboptimal numbers of EAE-effector cells: induction of chronic EAE in whole tissue-sensitized guinea pigs.
Authors: Driscoll B F , Kies M W , Alvord E C
Published: December 2022

Experimental allergic encephalomyelitis (EAE) in strain 13 guinea pigs is an acute monophasic disease induced with myelin basic protein (BP) in complete Freund's adjuvant (CFA). We report here that EAE can be effectively suppressed by transfer of a limited number of EAE-effector cells. Lymph node cells (LNC) from donors sensitized with BP/CFA are activated in vitro by incubation with BP and strain 2 peritoneal exudate cells (PEC). 5 X 10(7) of these cells are capable of inducing lethal EAE in recipients; 0.5 to 1 X 10(7) cells (a suboptimal transfer) effectively suppress EAE induction in animals subsequently sensitized with BP/CFA. Suppressed recipients develop an early mild disease from which they recover completely. In contrast, suboptimal transfer of BP-sensitized cells does not protect recipients against sensitization with whole central nervous system (CNS) tissue/CFA. About 50% of these recipients succumb to acute EAE; the survivors develop chronic EAE of varying intensity: a mild chronic form with recovery, a severe chronic form that is eventually fatal, and a chronic relapsing form that results in permanent neurologic deficit. Preliminary attempts at detecting suppressor cells in the suppressed animals were unsuccessful. Instead, PEC of all recipients of suboptimal transfers were capable of transferring EAE to naive animals.
Induction and persistence of local B cell memory in mice.
Authors: Baine Y , Thorbecke G J
Published: December 2022

Mice were injected with TNP-KLH in one front footpad and challenged in both front footpads 1 to 16 wk thereafter. The response of the contralateral node was significantly lower than that of the ipsilateral node early and again late, but not at intermediate, intervals after priming. This difference was not abolished by boosting with a higher dose of antigen or by administering excess carrier-primed helper T cells before challenge with antigen. The ipsilateral brachial lymph node cells transferred significantly higher B cell memory responsiveness at all intervals after priming than the contralateral lymph node, although at 2 to 4 wk both lymph nodes transferred substantial memory. At later intervals (more than 8 wk) only the ipsilateral lymph nodes transferred significant memory for TNP. Priming in the front footpads did not result in a splenic primary response, but a secondary response was observed in the spleen after boosting in the footpads. The relative importance of antigen localization and circulating memory cells in determining induction and persistence of memory in sites of lymphoid tissue proximal and distal to antigen injection is discussed.
New immunoglobulin IgG allotypes and haplotypes found in wild mice with monoclonal anti-allotope antibodies.
Authors: Huang C M , Parsons M , Wakeland E K , Moriwaki K , Herzenberg L A
Published: December 2022

Sera from 156 wild mice (Mus musculus L.) collected from parts of Eurasia, Northern Africa, and the Americas were tested in solid-phase radioimmunoassays for reactivity with 20 monoclonal anti-allotope antibodies directed against gene products of the Igh-1, Igh-3, and Igh-4 loci. Most of the wild mice have Igh phenotypes similar to those of inbred strains or heterozygotes thereof, but frequently the wild mice showed unique combinations of allotypes on a given chromosome (haplotypes) not seen in inbred strains. We found new allotypes of the Igh-1 and Igh-4 loci. Mice from three regions (Poland, Taiwan, and Japan) possess combinations of allotypes indicating that recombination, gene conversion, or other gene duplication events have occurred in portions of the Igh constant region gene complex. Most interestingly, sera of three mice from Egypt possess immunoglobulin molecules appearing to result from an intragenic recombination event involving either Igh-1d or Igh-3d with Igh-1b. Two mice from Pakistan and one from Seychelles Island in the Indian Ocean also showed similar unusual phenotypes. These mice possess two CH2 IgH-1b and two CH2 Igh-1a/CH2 Igh-1d determinants, suggesting that these variant immunoglobulin arose from recombinations within the CH2 domain.
Immunologic memory to phosphorylcholine. II. PC-KLH induces two antibody populations that dominate different isotypes.
Authors: Chang S P , Brown M , Rittenberg M B
Published: December 2022

We examined the fine specificity of the memory response to phosphorylcholine (PC) using an enzyme-linked immunosorbent assay (ELISA) that measures the relative abilities of PC analogs to inhibit the binding of antibody to antigen. Along with the usual haptens (phosphorylcholine, L-alpha-glycerophosphorylcholine, and choline) these studies included as an inhibitor p-nitrophenyl phosphorylcholine, a compound that is homologous to the structure of the PC antigen in a protein conjugate. Evaluation of the fine specificity profiles revealed two populations of antibody elicited by PC-KLH, which were unequally dominant among the various immunoglobulin classes and IgG subclasses. Group I antibodies exhibited a similar or slightly greater avidity for PC than for NPPC and constituted the majority of IgM, IgA, and IgG3 antibodies. Group II antibodies, which were expressed primarily by IgG1, IgG2a, and IgG2b antibodies, possessed significant avidity only for NPPC. Possible mechanisms that would link IgM, IgA, and IgG3 to similar variable regions while excluding IgG1, IgG2a, and IgG2b from the same grouping are discussed.
Characterization of suppressor cells regulating in vitro expression of IgG2A and IgG2B antibody responses.
Authors: Löwy I , Joskowicz M , Theze J
Published: December 2022

In vitro cooperative responses between hapten-primed anti-Thy-1.2 plus C-treated spleen cells and carrier-primed T cells have different isotypic patterns depending on the source of the T helper cells. T helper cells from primed lymph node induce IgG1, IgG2a, and IgG2b PFC responses, whereas T helper cells from primed spleen induce only an IgG1 type of response. The addition of activated spleen cells to the lymph node cells suppresses their ability to generate IgG2a and IgG2b PFC responses. The suppressor cells involved have been characterized. Functionally, they appear as nonantigen specific and isotype specific, because they never reduce the IgG1 response. They are Lyt-2.2 positive, Lyt-1 negative, and radiosensitive. Their relative resistance to anti-Thy-1.2 plus C treatment indicates that they express low amounts of this antigen or that they are heterogeneous concerning the expression of Thy-1.2.
Cytokine-dependent thymocyte responses: characterization of IL 1 and IL 2 target subpopulations and mechanism of action.
Authors: Conlon P J , Henney C S , Gillis S
Published: December 2022

The responsiveness of murine thymocytes to T cell mitogens was examined in the presence of highly purified preparations of IL 1 and IL 2. Fractionation of thymocytes by selective agglutination with peanut lectin (Arachius hypogeae) resulted in separation of two cell populations, each of which mediated distinctive responses to cytokine stimulation. The majority of thymus cells, agglutinated by the lectin (PNA+), were found to be unresponsive to mitogen in the presence of the macrophage-derived factor, IL 1; but showed marked proliferation when stimulated by mitogen in concert with the T cell-derived factor, IL 2. The nonagglutinated fraction, (PNA- cells) demonstrated substantial levels of proliferation after stimulation with mitogen in the absence of any exogenous factors. Moreover, IL 1 alone was highly mitogenic for PNA-thymocytes. This stimulation was further shown to result in the subsequent release of IL 2, as assessed by both the detection of IL 2 by lymphokine-dependent T cell lines and the inhibition of IL 1-dependent mitogenesis by the presence of anti-IL 2 monoclonal antibody. These results further substantiate the important immunoregulatory nature of these proteins and elucidates the possible role of these substances in the ontogeny of T cell responsiveness.
Helper factor production in murine secondary syngeneic mixed leukocyte reactions.
Authors: Zuberi R I , Altman A
Published: December 2022

Culture supernatants of murine thymocytes or spleen cells responding in a secondary syngeneic mixed leukocyte reaction (SMLR) were studied for their biologic effects on cell-mediated immune responses in vitro. Such supernatants contained helper factor(s) that facilitated the development of alloantigen-specific cytotoxic T lymphocyte (CTL) responses from thymocyte precursors. Thymocytes, but not spleen cells, required activation by allogeneic effect factor (AEF) in primary culture in order to proliferate and produce biologically active mediator(s) during a secondary SMLR. The same culture supernatants possessed, in some instances, weak T cell growth factor (TCGF; IL 2) activity. However, TCGF activity could be dissociated from helper factor(s) active in the CTL induction assay because some culture supernatants that had potent helper activity were devoid of TCGF activity. This lack of TCGF activity was not due to a lower degree of sensitivity of the TCGF assay or to the presence of a selective TCGF inhibitor in the SMLR-derived supernatants, indicating that the helper factor(s) studied is distinct from TCGF. Production of immunoregulatory lymphokines during the SMLR may serve as a physiologically relevant model for studying the role of T cell-derived lymphokines in immunoregulation.
Correlation of human neutrophil secretion, chemoattractant receptor mobilization, and enhanced functional capacity.
Authors: Fletcher M P , Seligmann B E , Gallin J I
Published: December 2022

Studies were performed to elucidate further the phenomenon of secretagogue-mediated enhancement in the binding of the chemoattractant f-met-leu-[3H]phe to human neutrophils (PMN). Specific f-met-leu-[3H]phe binding to unstimulated PMN reached maximum levels after 10 to 15 min of incubation at 0 degrees C with a saturating concentration of peptide, and consisted of a readily displaceable and a nondisplaceable component. PMN, preexposed to A23187 (2.5 X 10(-8) M) or PMA (0.5 ng/ml) for 30 min at 37 degrees C to stimulate limited and preferential release of specific (secondary) granules (10 to 20% of total lysozyme, no beta-glucuronidase), demonstrated an approximate doubling in the displaceable component of f-met-leu-["3H]phe binding, accompanied by an increasing nondisplaceable component that could not be explained by bulk pinocytosis of extracellular fluid (assessed by [3H]sucrose uptake). The increase in f-met-leu-[3H]phe binding was not affected by inhibitors of protein synthesis, could not be attributed to the secreted products lysosyme or lactoferrin acting on the cell, and, on the basis of studies with PMN from patients with chronic granulomatous disease, could not be attributed to the effects of reactive oxygen species generated in low concentration during stimulation. Functional studies on PMN indicated that preexposure to secretagogues at concentrations demonstrated to increase receptor availability also enhanced subsequent f-met-leu-phe-mediated superoxide and hydrogen peroxide generation. The present data demonstrate that secretagogues may activate PMN to enhance their subsequent responses in f-met-leu-phe-mediated processes, and, combined with previous reports, support the concept that specific granules provide a source of preformed membrane and receptor material that is translocated to the cell surface during the secretion associated with directed locomotion.
Studies on natural killer (NK) cells. III. The effects of in vitro culture on spontaneous cytotoxicity of murine spleen cells.
Authors: Bartlett S P , Burton R C
Published: December 2022

In vitro culture of normal lymphohemopoietic cells is a complex event leading to the generation of a diverse group of effector cells. When murine spleen cells are cultured by themselves in fetal calf serum containing medium for up to 9 days, at least 3 distinct subpopulations of cytotoxic effectors can be distinguished on the basis of tumor target cell preference and expression of cell surface alloantigens. Fresh spleen cell suspensions contain 2 distinct NK cell types: NK-1.2+ NKA cells, which preferentially lyse lymphoma targets, and NK-1.2- NKB cells, which lyse nonlymphoma, mainly solid tumor targets. These NK cells account for all the cytolytic activity on day 0 of culture. NK-1.2+ NKA cells are very labile, and greater than or equal to 80% of their activity is lost within 48 hr of culture. By contrast, the activity of NKB cells increases in culture, up to 4-fold by day 6, and solid tumor target cells resistant to lysis by fresh spleen cells now become susceptible. In addition, an NK-1.2-, H-2+, Thy-1.2+, Ly-1.2+, Ly-2.2+ cytotoxic effector cell arises in culture from, or is dependent upon the presence of, NK-1.2-, Thy-1.2+ cells. This spontaneously arising "Tc" has a peak of activity between day 3 and 6 of culture, and kills a variety of lymphohemopoietic tumor cell types.
Effect of a monoclonal anti-large granular lymphocyte antibody on the human NK activity.
Authors: Nieminen P , Paasivuo R , Saksela E
Published: December 2022

A monoclonal hybridoma antibody of IgGIa subclass was produced by fusing NS-1 myeloma cells with spleen cells of a mouse immunized with human LGL cells. This hybridoma antibody, termed NK-8, was reactive by indirect immunofluorescence with 33% of peripheral blood LGL cells and 70% of LGL forming conjugates with K-562 cells. Monocytes, granulocytes, and other lymphocytes were nonreactive. In iodinated protein A binding assays NK-8 was nonreactive with all kinds of leukemia and lymphoma lines tested and showed activity only against LGL cells. NK-8 inhibited the LGL-mediated cytotoxicity against K-562 cells by 50 to 60% without complement and inhibited the K-562 induced interferon production from the LGL population. However, the spontaneous cytotoxicity against human skin fibroblasts was augmented if the effector cells were pretreated with NK-8.
Ligand-induced association of surface immunoglobulin with the detergent-insoluble cytoskeletal matrix of the B lymphocyte.
Authors: Braun J , Hochman P S , Unanue E R
Published: December 2022

Ligand binding is believed to induce surface immunoglobulin (Ig) to form a physical association with the underlying cell cytoskeleton. We investigated this interaction by use of nonionic detergents, which are known to dissolve membrane proteins but preserve a detergent-insoluble cytoskeletal residue. In the absence of ligand treatment, surface Ig in the B cell plasma membrane was fully dissolved by nonionic detergent; however, interaction with a ligand converted the receptor to a novel, detergent-insoluble state. The conversion of surface Ig to a detergent-insoluble form required receptor cross-linking but occurred independently of capping. Several types of experiments demonstrated that this form of Ig was not due to the size insolubility of immune complexes and involved a stable, noncovalent association of the receptor with the detergent-insoluble, cytoskeletal residue. Incubation of ligand-bound cells at 37 degrees C promoted the degradation of surface Ig and the appearance of new, lower m.w. species, including a major soluble protein (50,000 daltons) that was antigenically related to surface Ig. These events corresponded to receptor endocytosis by several criteria (time course, temperature sensitivity, and energy dependence). Taken together, these results were consistent with the ligand-induced transmembrane attachment of receptors to the underlying cytoskeletal matrix followed by receptor internalization and catabolism.
A ganglioside-dependent cellular binding mechanism in rat macrophages.
Authors: Riedl M , Forster O , Rumpold H , Bernheimer H
Published: December 2022

A rosetting assay was performed with rat alveolar and peritoneal macrophages and sheep red blood cells (SRBC) treated with gangliosides. SRBC incubated with GM2, GD1a, and a mixture of bovine brain gangliosides (BBG) showed binding to rat macrophages. The extent of binding was dependent on the concentration of gangliosides. Binding induced by GM2 was stronger than that induced GD1a and BBG. GM1 and GA2 did not induce rosette formation. Inhibition studies with gangliosides, sialyllactose, lactose, and neuraminic acid suggested that the macrophage binding site recognizes neuraminic acid in conjunction with neighboring carbohydrates showing highest affinity for GM2. Sodium azide, sodium fluoride, ethylenediaminetetraacetate, cytochalasin B, and colchicine did not inhibit rosette formation. The percentage of peritoneal macrophages binding ganglioside-treated SRBC was lower than that of alveolar macrophages. Proteose-peptone-stimulated peritoneal macrophages, however, showed an increase of rosette formation. Around 30% of adherent spleen cells also had binding activity for GM2-treated SRBC. Peripheral blood mononuclear cells did not bind ganglioside-treated SRBC. Phagocytosis of GM2-treated SRBC attached to alveolar macrophages could not be observed. It is suggested that macrophages may express recognition sites for certain gangliosides that might be important in cell-cell interaction.
Restoration of T cell depression and suppression of blood pressure in spontaneously hypertensive rats (SHR) by thymus grafts or thymus extracts.
Authors: Ba D , Takeichi N , Kodama T , Kobayashi H
Published: December 2022

Spontaneously hypertensive rats (SHR) that develop hypertension and arterial lesions resembling human periarteritis nodosa were found to possess a selective depression of T cell functions with an appearance of natural thymocytotoxic autoantibody (NTA). The relationship between T cell depression and hypertension in these animals was investigated. The immune responsiveness of T cell-depressed SHR was completely recovered by histocompatible thymus grafts and was partially restored by histoincompatible allogeneic or xenogeneic thymus grafts or by injection of thymus extracts. Transplantation of compatible thymus tissues into neonatal SHR produced long-lasting recovery of immune functions. When complete immunologic restoration was achieved, significant suppression of high blood pressure was obtained. The SHR that showed high blood pressure were always accompanied with high NTA titers and arterial lesions. Thymus grafts or thymus extracts significantly decreased the titers of NTA. The development and dissemination of arterial lesions, which may cause increased blood flow resistance, were completely prevented by compatible thymus grafts into neonatal SHR. These results suggest that thymus grafts and thymus extracts may suppress the development of hypertension by preventing or curing the periarteritis nodosa in SHR.
Switch from NP-specific IgG3 to IgG1 in the mouse hybridoma cell line S24/63/63.
Authors: Baumhäckel H , Liesegang B , Radbruch A , Rajewsky K , Sablitzky F
Published: December 2022

We have isolated by fluorescence-activated cell sorting an IgG1 expressing class switch variant (S24-1/47) from the IgG3-producing mouse hybridoma cell line S24/63/63. Both Ig bind the hapten 4-hydroxy-3-nitro-phenylacetyl (NP) with approximately the same affinity and fine specificity and are idiotypically indistinguishable. The apparent m.w. is 50,000 for the gamma 1 and 51,000 for the gamma 3 chain. The genomic DNA of IgG3-producing S24/63/63 cells contains a 14-kb Eco RI restriction fragment with C gamma 3 sequences representing a rearranged C gamma 3 gene. In the class switch variant S24-1/47 the C gamma 3 gene is deleted.
A new complement-dependent bactericidal factor found in nonimmune mouse sera: specific binding to polysaccharide of Ra chemotype Salmonella.
Authors: Ihara I , Harada Y , Ihara S , Kawakami M
Published: December 2022

It has been shown that nonimmune mouse sera contain a complement-dependent bactericidal factor that reacts specifically with Ra chemotype Salmonella. In this study we investigate a specific determinant to which this factor binds. This factor bound to Ra chemotype lipopolysaccharide (LPS) but not to S or Re chemotype LPS. The binding was markedly inhibited by N-acetyl-D-glucosamine (GlcNAc), which was the nonreducing terminal of the Ra polysaccharide chain and by certain monosaccharides structurally relating to L-glycero-D-mannoheptose, a terminal component of a side branch of Ra polysaccharide. The factor bound to the Ra bacteria could be eluted with a medium containing GlcNAc. These results indicate that the specific determinant is the polysaccharide region of LPS characteristic of Ra chemotype Salmonella. Ca2+ but not Mg2+ was required for the specific binding of the factor to cells of Ra bacteria. A molecule composed of a polypeptide of 28,000 m.w. was found in the active fraction obtained by the monosaccharide elution. However, no polypeptides corresponding to light and heavy chains of mouse immunoglobins were detected from the active fraction.
Human host response to Giardia lamblia. I. Spontaneous killing by mononuclear leukocytes in vitro.
Authors: Smith P D , Elson C O , Keister D B , Nash T E
Published: December 2022

To understand host resistance to Giardia lamblia infection, we investigated the capacity of human peripheral blood effector cells to kill G. lamblia trophozoites. Peripheral blood was obtained from 12 healthy, uninfected individuals without detectable IgG anti-G. lamblia antibody or known exposure to G. lamblia. Isolated mononuclear leukocytes (MNL), granulocytes, lymphocytes, and monocytes were cultured 16 hr with G. lamblia that had been pulsed with (3H)TdR while in log growth. MNL from all 12 individuals were spontaneously cytotoxic for G. lamblia. Specific cytotoxicity ranged from 13% at an E:T of 3:1 to 56% at an E:T of 100:1. Release of 3H directly correlated with a decrease in viable G. lamblia. In contrast to the uniform cytotoxicity by mononuclear cells, granulocytes and lymphocytes had no spontaneous cytotoxic activity for G. lamblia. MNL depleted of phagocytic or adherent cells lost all cytotoxic activity. Also, G. lamblia induced nonspecific MNL cytotoxicity to unrelated target cells. Finally, cytotoxicity against G. lamblia could be inhibited by adding unlabeled Trichomonas vaginalis, suggesting that this may be a more general mechanism of host defense against extracellular protozoa. We conclude that human peripheral blood monocytes-macrophages are spontaneously cytotoxic for G. lamblia and that this may be a major mechanism of host defense against this parasite.
Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT4+ population belong to a distinct subset.
Authors: Thomas Y , Rogozinski L , Irigoyen O H , Shen H H , Talle M A , Goldstein G , Chess L
Published: December 2022

In the present report, we characterize a monoclonal antibody directed at a surface differentiation antigen on human T cells. The monoclonal antibody, OKT17, recognizes a cell surface antigen present on the majority of resting normal peripheral T cells. In contrast, OKT17 is unreactive with normal B cells, B cell lines, T cell lines, or SIg+ CLL. Interestingly, after activation, the antigen recognized by OKT17 is lost from a subset of OKT4+ cells. We took advantage of this finding to explore further the functional heterogeneity within activated OKT4+ cells. Evidence was obtained that the PWM-activated OKT4+ subset remaining after depletion of OKT17-reactive T cells (OKT4+ 17-) contains radiosensitive helperr cells but is devoid of suppressor cells. In contrast, the activated OKT4+ 17+ population contains potent radiosensitive suppressor cells as well as radioresistant helpe cells. Taken together, these studies suggest that the OKT17 monoclonal antibody can differentiate two functionally mature, activated OKT4+ human T cells: OKT4+ OKT17+ radiosensitive suppressor cells and OKT4+ 17- radiosensitive helper cells.
Conformational changes in complement component C4 induced by activation, treatment with amines, chaotropes, or freezing-thawing, detectable by radioiodination using lactoperoxidase.
Authors: von Zabern I , Gigli I
Published: December 2022

Conversion of C4 to C4b by enzymic cleavage or generation of a C4b-like form by treatment with amines, chaotropes, or freezing and thawing is accompanied by conformational alterations in the molecule. The nature of the changes is the same whether C4 is converted to a C4b-like form or to C4b. Evidence for structural changes at the surface of the C4 molecule was obtained by peripheral labeling with 125I by the lactoperoxidase method: there are residues, probably tyrosines, that are inaccessible for radioiodination in C4b and C4b-like C4, but exposed in native C4. The residues concerned are located in two separated parts of the alpha-chain at a distance of approximately 9000-34,000 m.w. from the N-terminus and in a 16,000 m.w. portion at the C-terminus. It is so far unknown whether the observed changes are involved in the uncovering of new binding sites, or whether they are the mere reflection of alterations elsewhere in the molecule that are of greater functional significance.
Control of macrophage Ia expression in neonatal mice--role of a splenic suppressor cell.
Authors: Snyder D S , Lu C Y , Unanue E R
Published: December 2022

The control of macrophage expression of I region-associated antigens (Ia) in neonatal mice was studied by comparing responses of neonatal and adult mice to immune vs nonimmune stimuli. Adults generated peritoneal exudates rich in Ia-bearing macrophages in response to i.p. injection of live Listeria monocytogenes, Listeria-immune T cells, and heat-killed Listeria, or a soluble mediator termed macrophage Ia-recruiting factor (MIRF). Neonates failed to respond to these stimuli. In contrast, both neonates and adults generated Ia-negative peritoneal exudates when stimulated with thioglycollate. A neonatal spleen cell that blocked the response of adults both to immune T cells and heat-killed Listeria and to MIRF was identified and characterized. Some of the suppressor cells appeared to be early precursors of the phagocytic lineage that develop into mature monocyte-macrophages. Suppression was apparently mediated by metabolites of arachidonic acid since indomethacin and aspirin in vivo blocked the effect. Similar suppressor activity was found in adult bone marrow and in adult resident peritoneal exudate cells. Thus, the phagocytic line autoregulates its surface expression of Ia in both neonatal and adult mice. This mechanism becomes particularly pointed during early development and could contribute to the lack of immunity during ontogeny.
Lymphokine modulation of fibroblast proliferation.
Authors: Nielson E G , Phillips S M , Jimenez S
Published: December 2022

In an experimental model of interstitial nephritis resulting in fibrosis, lymphokines secreted by a common population of antigen-reactive T lymphocytes have been shown to exert a bidirectional influence on fibroblast proliferation and collagen synthesis. We report that these lymphokines can be chromatographically separated into two fractions. The larger m.w. fraction stimulated fibroblast proliferation whereas the smaller m.w. fraction was inhibitory. These results further clarify potentially important immune regulators of fibrogenesis.
Prolonged suppression of experimental allergic encephalomyelitis in the Lewis rats: the effect of lipopolysaccharides.
Authors: Raziuddin S , Morrison D C
Published: December 2022

The current investigations have revealed that Lewis rats preimmunized with BP in CFA, and after recovery from the first episode of EAE, developed a second mild attack of EAE after challenge with BP/CFA at specified times. However, preimmunization of Lewis rats with BP complexed to LPS in CFA protects animals for a longer time from a second attack induced by BP/CFA challenge.
A monoclonal antibody detecting unusual Thy-1 determinants.
Authors: Auchincloss H , Ozato K , Sachs D H
Published: December 2022

20-10-5S is a monoclonal antibody produced by the fusion of C3H anti-C3H.SW splenocytes with the SP2/0 cell line. The antibody appears to react with Thy-1 determinants by several criteria including cytotoxicity patterns, functional assays, genetic analyses, and competitive binding experiments. However, the antibody and the determinants it detects are unusual in that: 1) 20-10-5S is autoreactive; 2) the antibody shows allospecificity for Thy-1.2 vs Thy-1.1 antigens only on peripheral lymphocytes and not on thymocytes; and 3) the antibody reacts only with determinants on murine T cells and not with antigens on brain tissue or on rat thymocytes. It therefore seems that 20-10-5S reacts with murine T cell-specific Thy-1 determinants that are lost or modified during maturation of the cells on which they are expressed.
In vitro and in vivo allogeneic effects: differential modulation of B cell subpopulations.
Authors: Golding H , Rittenberg M B
Published: December 2022

We examined the sensitivity of primary TD and TI responses to allogeneic effects and found that primary TD responsive B cells were very sensitive to negative allogeneic effects elicited in vitro. The primary TI-2 responses, on the other hand, were not suppressed but rather enhanced twofold to threefold under the same culture conditions. Thus, primary B cell subsets resemble their IgG memory counterparts (1) in their differential sensitivity to allogeneic T cells. The ability of in vivo induced allogeneic effects of modulate antibody responses was studied using chronic graft-vs-host reaction (GVH) as a model. F1 mice immunized with TD (TNP-KLH, TNP-sheep-gamma-globulin) antigens shortly after GVH induction had reduced IgM and IgG primary responses. In contrast, the primary response to TNP-Ficoll was enhanced and included a large number of primary IgG PFC. Furthermore, mice undergoing chronic GVH were incapable of developing long-term memory after immunization with a TD antigen (TNP-KLH), as determined by secondary in vitro challenges with either TD or TI antigens. These mice retained helper T cells, indicating a failure of memory development in the B cell compartment. These studies suggest that the secondary TD- and TI-responding precursors (B2 gamma and B1 gamma, respectively) are probably both derived from primary B2 precursors (which are very sensitive to negative allogeneic effects). The maturation of the B1 memory population may thus be linked to increased resistance to allosuppression.
Regulation of macrophage populations. IV. Modulation of Ia expression in bone marrow-derived macrophages.
Authors: Calamai E G , Beller D I , Unanue E R
Published: December 2022

The expression of I region-associated (Ia) antigens was studied in macrophages derived from bone marrow cell precursors cultured in L cell-conditioned medium (LCM) as a selective growth stimulator. Very few macrophages expressed Ia either while growing actively in LCM or when quiescent, after the removal of LCM from the culture. The addition of T cell lymphokines, however, stimulated the biosynthesis and membrane expression of Ia. Uptake of bacteria by the macrophage during exposure to the lymphokines produced a synergistic increase in Ia expression. The lymphokine-induced stimulation of Ia was reduced by the simultaneous presence of LCM, suggesting that growth and differentiative stimuli have opposing effects on Ia induction. All macrophage colonies derived from single precursors contained cells that could be induced to express Ia.
Identification and molecular characterization of macrophage-associated antigens of the rat.
Authors: Veit B C , Hamilton T A , Kotb M
Published: December 2022

Rabbit antiserum to rat peritoneal exudate (PE) macrophage (M phi) antigens was prepared and its reactivity with cell surface proteins of M phi, granulocytes, and lymphocytes was studied by one- and two-dimensional polyacrylamide gel electrophoresis (PAGE). A total of 14 membrane antigens were identified of which three were found to be expressed only by M phi and granulocytes. By one-dimensional analysis, a protein with an approximate m.w. of 105,000 was present on splenic and PE M phi and on splenic lymphocytes. Two-dimensional analysis revealed that this band was heterogeneous and contained at least three species, one of which was restricted to expression on M phi and granulocytes. A second protein of 150,000 daltons was resolved into two species by two-dimensional analysis. Both of these species were present on M phi and granulocytes but not on lymphocytes. Both the 105,000- and 150,000-dalton proteins were glycosylated. Because the 105,000- and 150-000-dalton proteins expressed by M phi were also expressed by granulocytes, is is likely that these are differentiation antigens whose expression is a characteristic property of cells within both monocytoid and myeloid lineages. All three 105,000-dalton species and one of the two 150,000-dalton species were detected on mouse M phi, indicating their expression is not unique to the rat.
Structural analysis of thymus-leukemia (TL) antigens in the mouse.
Authors: McIntyre K R , Hämmerling U , Uhr J W , Vitetta E S
Published: December 2022

Thymus-leukemia (TL) antigens have been sequentially immunoprecipitated from glycoprotein pools prepared from lysates of biosynthetically labeled ASL-1w leukemia cells with a monoclonal antibody and a standard alloantiserum. Results suggest that on leukemia cells from Tlaa mice, as previously reported for thymocytes from these mice, all the alloantiserum-defined TL specificities (TL.1, 2, 3, 5, 6) as well as the specificity defined by the monoclonal antibody (TL.m3) are carried by a single molecular species. The degree of structural homology between the 45,000-m.w. heavy chains of TL and H-2 was investigated by the technique of comparative tryptic peptide mapping. Results indicate that TL is more distantly related at the primary structural level to H-2 than H-2 antigens are to one another.
Studies on the mechanism of NK cell lysis.
Authors: Quan P C , Ishizaka T , Bloom B R
Published: December 2022

The mechanism of cytolysis by murine NK cells was analyzed using a variety of metabolic inhibitors that have proven informative in studying the lytic mechanism of CTL and the mechanism of histamine release by mast cells. Target cell binding occurred in the absence of calcium and was inhibited by only one of the agents studied, cytochalasin B. Lysis was initiated by addition of Ca2+ ions, as in the case of CTL. Subsequent to target cell binding, but prior to programming for lysis by Ca2+, NK cell lytic activity could be suppressed by inhibitors of chymotrypsin-like, but not trypsin-like proteases, in contrast to CTL. In addition, 3-deaza-SIBA, an inhibitor of transmethylation reactions and quinacrine, an inhibitor of phospholipase A2, appear to act before the Ca2+-dependent programming for lysis. Sr2+ ions blocked the lytic function, as did trifluoperazine (stelazine), the former presumably competing for ionic calcium, the latter known to block binding of Ca2+ to calmodulin. 8Br-cAMP and colchicine blocked later steps required for lysis. With the possible exception of trifluoperazine, all of the agents that blocked NK cell lysis are known to inhibit histamine release from mast cells. These results lend support to the stimulus-secretion model, originally proposed to explain the mechanism of CTL cytolysis, as relevant to the mechanism of lysis by NK cells.
Monocyte aggregation and superoxide anion release in response to formyl-methionyl-leucyl-phenylalanine (FMLP) and platelet-activating factor (PAF).
Authors: Yasaka T , Boxer L A , Baehner R L
Published: December 2022

Like the PMN, human peripheral blood monocytes were capable of aggregating in response to FMLP and PAF. Monocyte aggregation was dependent on glycolysis and the presence of divalent cations. Unlike the PMN, monocyte aggregation in response to FMLP was not accompanied by degranulation, nor was it potentiated by cytochalasin B. Furthermore, cytochalasin B and its cogenitor, dihydrocytochalasin B, inhibited aggregation in response to PAF. PAF and FMLP appeared to react with the monocyte at separate receptors because sequential challenge of the monocyte with the same agents failed to elicit further aggregation, whereas rechallenge with the alternative agent induced further aggregation. Because the monocyte will aggregate to chemotactic agents in vitro, it is likely that the cell will be affected by these agents in vivo, which could lead to leukoembolization of circulating monocytes.
Effect of mouse anti-I region antiserum and complement on human mononuclear cell response to concanavalin A.
Authors: Campbell D A , Oehler J R , Tsai C T , LoBuglio A F , Niederhuber J E
Published: December 2022

Pretreatment of human peripheral blood mononuclear cells with mouse anti-Ia serum and complement was found to inhibit the subsequent T cell proliferative response to Con A. The cells from each individual tested were inhibited, regardless of DR allospecificity. Inhibition of Con A response by mouse anti-Ia antibodies and C was found to be due to elimination of adherent accessory cells (monocytes) rather than T cells. Anti-Ia serum appeared to recognize an essential subpopulation of human monocytes bearing cross-reactive antigens, since not all monocytes treated with anti-Ia serum and C were lysed. The use of highly restricted mouse anti-Ia serum demonstrated that the required monocyte population expressed antigens recognized by antibodies with activity to I-Ek products (Ia specificities Ia.7 and Ia.22). The required monocyte subpopulation was also recognized by a monoclonal antibody specific for Ia.7. Mouse anti-I-Ek alloantiserum or monoclonal anti-Ia.7 antibodies may be important tools with which to study human monocytes, and for further characterization of DR determinant requirements for monocyte-antigen presentation and monocyte-T cell interactions.
Antigen-specific. I region-restricted interactions in vitro between tumor cell lines and T cell hybridomas.
Authors: Walker E , Warner N L , Chesnut R , Kappler J , Marrack P
Published: December 2022

A series of H-2d B cell tumor lines and one monocytic tumor cell line were shown to be capable of I region-restricted antigen presentation to I-A-d- and I-Ed- restricted, antigen-specific cloned T cell hybridomas. For the most part, antigen presentation correlated with the present of Ia antigens on the presenting cells, although in a few interesting cases Ia-expression lines failed to present antigen. These T cell hybridomas, together with the B cell and to monocyte tumor cell lines, offer a unique set of tools to study the phenomenon of I region-restricted antigen presentation.
Regulation of macrophage-mediated suppression by purine nucleoside phosphorylase substrates.
Authors: Cohen A , Kimchi Z
Published: December 2022

Thymuses from dexamethasone-treated rats contain macrophage-like cells that completely suppress the proliferative response of thymocytes to concanavalin A. This macrophage-mediated suppression is abolished by low concentrations of purine nucleoside phosphorylase (PNP) substrates: deoxyguanosine (20 microM), guanosine (100 microM), and deoxyinosine (250 microM). Similar effects were observed when resident peritoneal macrophages were used. Deoxyguanosine regulates suppression by acting directly on macrophages. The mode of deoxyguanosine action on macrophages does not involve its phosphorylation and incorporation into deoxynucleotide pools. The significance of this regulation of macrophage-mediated suppression by PNP substrates to immune regulation in normals and in PNP-deficient patients is discussed.
Genetic control of the cytolytic T lymphocyte response to influenza viruses: H-2 genes influence the response to H-2Kb plus virus.
Authors: Reiss C S , Dorf M E , Benacerraf B , Burakoff S J
Published: December 2022

Genetic control of the cytolytic T lymphocyte responses to influenza virus was examined. Mice bearing the H-2b haplotype and F1 hybrid mice derived from C57BL/6 parents failed to recognize H-2Kb plus type A or type B influenza viruses. Congenic mice that shared H-2Kb but had either H-2Dd of H-2Dq genotypes responded in in vitro secondary cultures to H-2Kb plus virus. Mapping studies suggest the gene(s) controlling the ability to respond to H-2Kb plus virus can be localized in or near the H-2D region. Several interpretations of these observations are discussed.
Lymphocytes bearing Fc receptor for IgE. VIII. Affinity of mouse IgE for Fc epsilon R on Mouse B lymphocytes.
Authors: Vander-Mallie R , Ishizaka T , Ishizaka K
Published: December 2022

Fc epsilon R(+) lymphocytes were demonstrated in BALB/c, C57BL/6 and SJL strains of mice by a rosetting technique. The proportion of Fc epsilon R(+) lymphocytes in their spleens was 25 to 33% of the total cells. The majority of the Fc epsilon R(+) cells in the spleen of BALB/c mice were B cells, which also have Fc gamma R. However, after infection of mice with Nippostrongylus brasiliensis, a significant proportion of T cells also bore Fc epsilon R. The average number of Fc epsilon R per Fc epsilon R(+) cell in normal BALB/c spleens was 5100. These receptors were saturated with IGE after incubation of the cells with 5 micrograms/ml mouse IgE. The forward rate constant (k1) of the IgE binding to Fc epsilon R on normal B cells was 1.66 X 10(4) M-1 sec-1, while the dissociation rate of IgE from the Fc epsilon R was 1.7 x 10(-4) sec-1. The equilibrium constant between mouse IgE and Fc epsilon R on normal B cells was approximately 0.95 X 10(8)M-1. However, Fc epsilon R on mouse lymphocytes appeared to be heterogeneous with respect to their affinity for IgE. After infection of mice with Nippostrongylus brasiliensis, the number of Fc epsilon R per receptor-bearing lymphocyte increased several-fold. The FC epsilon R newly expressed after infection appeared to have a lower affinity for IgE than those present originally.
Complement (C3b) interaction with the human granulocyte receptor: correlation of binding of fluid-phase radiolabeled ligand with histaminase release.
Authors: Melamed J , Arnaout M A , Colten H R
Published: December 2022

The interaction of C3b, the major cleavage product of C3, with its receptor on human granulocytes results in important biological functions, including phagocytosis, superoxide generation, and release of a variety of enzymes, including histaminase. We have determined the binding kinetics and isotherm of trypsin-generated fluid-phase dimeric C3b at both 0 degrees C and 37 degrees C using human polymorphonuclear leukocytes (PMN). At 37 degrees C the apparent number of receptors per cell was threefold greater than number at 0 degrees C (66,000 vs 21,000), and the affinity (Ka) was slightly less (3.5 X 10(7) M-1 vs 6 x 10(7) M-1). C3b dimer binding was specifically inhibited by a F(ab,)2 anti-C3b receptor antibody. C3b dimer induced histaminase release in a dose-dependent fashion at a concentration of 1 to 4 X 10(7) molecules/cell, whereas at lower concentrations a dose-dependent inhibition of opsonized zymosan-induced release was noted. These effects were independent of IgG. In contrast, C3b monomer failed to demonstrate measurable direct binding or to induce histaminase release. Histaminase release, however, did occur after incubation of PMN with affinity-linked monomer (anti-C3 F(ab')2-C3b complexes). Monovalent complexes did not affect release. Monomeric C3, C3c, and C3d were without effect; however, affinity-linked C3 and C3c did cause release.
Ia.W39 expression correlates with a specific Ir function.
Authors: Huber B T , Hansen T H , Skelly R R , Thorley-Lawson D A
Published: December 2022

The xid- defective mouse (N X B6)F1 male and the I-Ab mutant of the B6 mouse bm12 have mutations on different chromosomes, and therefore in separate genes. However, both variant strains have a trait in common; namely, they are unresponsive to the A chain loop determinant(s) of beef insulin to which mice of the H-2b haplotype respond. We show here that in both mutant strains, this unresponsiveness is concurrent with the absence of the Ia.W39 specificity from the M phi and B cell surface. The concordance is specific for Ia specificity W39 and no other Ia determinant, suggesting that Ia.W39 is identical with the Ir epitope necessary for generating an immune response to a particular amino acid sequence of beef insulin. In the xid-defective mouse, the molecule carrying this antigen is synthesized but not expressed on the plasma membrane, presumably because a mature M phi and B cell subset is missing. By comparison, the bm12 mouse has mature B lymphocytes, but is unable to synthesize Ia.W39. Thus, bm12 has a structural mutation in the gene coding for Ia.W39, whereas xid is a mutant regulatory or maturation gene controlling the membrane expression of Ia.W39.