bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitors of DNA synthesis produced by herpesvirus-transformed cell lines.
Authors: Beneke J , Pearson G R
Published: December 2022

Inhibitory factors were detected in the supernatant fluids of two herpesvirus-transformed lymphoid cell lines, one a B cell line established from a cotton-topped marmoset with EBV-induced lymphoma (1605L) and the other a HVS-transformed marmoset T cell line (C-1 Ax). The factors produced by both cell lines inhibited the uptake of 125I-iododeoxyuridine (125I-IUDR) by lymphocytes stimulated by both phytohemagglutinin and pokeweed mitogen. Both factors also suppressed the uptake of 125I-IUDR by cells of lymphoid cell lines of both B and T cell origin, indicating that neither factor was specific for lymphoid subpopulations. Furthermore, the factor produced by the 1605L cell line did not exhibit tissue specificity in the target cells that it affected, since it also suppressed 125I-IUDR uptake by the HEp-2 cell line, which is epithelial. Antibody-dependent cellular cytotoxicity, an assay that has been reported to require effector cells capable of protein synthesis but not DNA synthesis, was not suppressed by either factor, indicating that these inhibitors acted at the level of DNA synthesis. Experiments investigating the kinetics of the inhibition of PHA blastogenesis by the 1605L factor suggested that this inhibitor blocked an early stage in the DNA synthetic cycle, since maximum inhibition was observed only when the factor was present early in the culture period.
Regulatory role of IgE-binding factors from rat T lymphocytes. I. Mechanism of enhancement of IgE response by IgE-potentiating factor.
Authors: Suemura M , Yodoi J , Hirashima M , Ishizaka K
Published: December 2022

T lymphocytes in the mesenteric lymph nodes of rats infected with Nippostrongylus brasiliensis spontaneously released a soluble factor that selectively potentiated the IgE-forming cell response of antigen-primed cells to homologous antigen. The factor could enhance the IgE response of DNP-OA-primed cells to DNP-HSA and T cell-replacing factor. In contrast, the treatment of OA-primed T cells with the factor failed to enhance either the IgE or IgG response of the mixture of DNP-KLH primed cells and OA-primed T cells to DNP-OA. The results collectively suggested that the target cells of the IgE-potentiating factor are B cells. Indeed, IgE potentiating factor was absorbed by B cells rather than T cells or thymocytes. Evidence was obtained that IgE-potentiating factor could be absorbed by IgE-bearing B cells or IgE-coupled Sepharose, indicating that the factor had affinity for IgE. It appeared that the potentiating factor bound to IgE-bearing B cells and selectively enhanced the differentiation of IgE-B cells to IgE-forming cells. It was also found that the major source of the factor was Fc epsilon R-bearing T cells.
Regulation of experimental allergic encephalomyelitis. II. Appearance of suppressor cells during the remission phase of the disease.
Authors: Welch A M , Holda J H , Swanborg R H
Published: December 2022

Lewis rats are susceptible to experimental autoimmune encephalomyelitis (EAE). Most rats recover from paralysis and are subsequently resistant to the disease. In an adoptive transfer system, we found that lymph node cells (LNC) from rats that had recovered from EAE protect syngeneic recipients from the disease when the latter are challenged with encephalitogenic myelin basic protein and adjuvant after receiving donor cells. Suppression is antigen-specific and requires viable LNC. In contrast to the suppressor cells we previously studied in tolerized rats, which were nonadherent T lymphocytes, the suppressor cells found in rats that have recovered from EAE adhere to glass wool. However, they are not retained on Sephadex G-10 columns to which macrophages adhere. Suppressor activity is enriched in the nylon wool-adherent LNC population (which consists of approximately 80% Ig+ cells). Our findings suggest that activation of adherent suppressor cells may be implicated in recovery from EAE. These may be adherent T cells, or B cells that produce anti-BP blocking antibodies.
The role of monocyte factors in the differentiation of immunoglobulin secreting cells from human peripheral blood B cells.
Authors: Rosenberg S A , Lipsky P E
Published: December 2022

Supernatants from cultures of human mononuclear phagocytes (M phi) were found to support pokeweed mitogen- (PWM) induced generation of immunoglobulin-secreting cells (ISC) in cultures of T cell-depleted, human peripheral blood B cells. The M phi factor did not augment PWM-stimulated B cell proliferation. Moreover, M phi factor itself was not a polyclonal B cell activator, in that no ISC were generated unless PWM was present in the B cells cultures. M phi factor release, however, did not require PWM stimulation, but occurred spontaneously under standard conditions used to elicit the PWM response. The active factor found in M phi culture supernatants originated from M phi and not from the few contaminating T cells in the M phi population. M phi factor did not replace the requirement for T cells in this system, however, since factor activity was apparent only when B cell cultures contained a small number of T cells. Finally, M phi factor augmented generation of both IgM and IgG ISC. These data emphasize the important role of M phi in the differentiation of human B cells into ISC and indicate that at least some of the function of M phi in this system is accomplished by secreted factors.
Specific induction of syngeneic cytotoxic T lymphocytes by solubilized tumor antigen: fractionation of the specific R-MuLV-induced leukemia antigen.
Authors: Alaba O , Law L W
Published: December 2022

The parameters of the secondary in vitro generation of syngeneic CTL by solubilized tumor antigens have been investigated. With PM and SPM, stimulation was achieved over a 10-fold antigen concentration, 5 microgram/ml to 0.5 microgram/ml, and with whole cells the optimum R/S cell ratio was 80:1 to 100:1. Assuming a 50-fold enrichment of plasma membrane antigens over cells by purifying the PM, this observation suggests that cells are at least 200 times more efficient than PM. A specific tumor antigen that induces CTL in vitro was solubilized with sodium deoxycholate and fractionated on Ultrogel AcA34 followed by affinity chromatography on Lens culinaris lentil lectin-Sepharose 4B column. The purification scheme was shown to have enriched for the specific CTL-inducing activity. The specificity of the induction and effector phases of the reaction was assessed and the data clearly indicate that the reactions were specific. Furthermore, we ruled out the possibility that the induction of CTL by soluble tumor antigen in a secondary reaction could be due to the nonspecific induction of helper activity, which then caused a polyclonal expansion of memory cells.
Elicitation of anti-viral cytotoxic T lymphocytes with purified viral and H-2 antigens.
Authors: Hale A H , Ruebush M J , Harris D T
Published: December 2022

The minimal molecular requirements for elicitation of secondary anti-Sendai virus CTL were investigated. The hemagglutinin-neuraminidase (HN) glycoprotein of Sendai virus and the H-2Kk glycoprotein of YAC tumor cells were purified and incorporated into phospholipid vesicles. These unilamellar liposomes were then tested for the ability to elicit H-2 restricted secondary anti-Sendai virus CTL. The results indicate that these well-defined vesicles were capable of eliciting secondary anti-Sendai virus CTL which lysed only target cells possessing the H-2Kk haplotype and modified with inactivated Sendai virus.
Ultrastructural evidence for release of major basic protein-containing crystalline cores of eosinophil granules in vivo: cytotoxic potential in Crohn's disease.
Authors: Dvorak A M
Published: December 2022

Eosinophil MBP-containing granule losses, cytotoxic tissue changes, primarily affecting autotomic nervous system axons, and degranulating mast cells were present in tissues from patients with Crohn's disease. These findings support the hypothesis (9) that the eosinophil may produce damage to cells of the gastrointestinal tract in Crohn's disease.
The murine macrophage Fc receptor for IgG2b is lipid dependent.
Authors: Anderson C L
Published: December 2022

The plasma membrane Fc receptor for IgG2b on P388D1 cells, solubilized by detergent, was inactivated by incubation with phospholipase C. Soluble Fc receptor activity could be restored by the addition of liposomes of either phosphatidylethanolamine or phosphatidylinositol. The reconstituted Fc receptor was trypsin sensitive. These data indicate that Fc receptor binding of IgG2b results from the concerted action of membrane lipid and protein.
Analysis of thymus-leukemia (TL) antigens with monoclonal antibodies.
Authors: McIntyre K R , Vitetta E S , Hämmerling U , Michaelson J , Flaherty L , Uhr J W
Published: December 2022

Lysates of radioiodinated thymocytes have been sequentially immunoprecipitated with monoclonal antibodies specific for thymus-leukemia (TL) antigens. The TL antigenic specificities defined by the monoclonal antibodies appear not to correspond precisely to specificities previously defined with conventional alloantisera. Nonetheless, each of two monoclonal antibodies specific for a single TL determinant was found to deplete lysates of B6.Tlaa thymocytes of all molecules precipitable by an alloantiserum specific for the conventionally defined determinants TL.1,2,3,5, and 6. These results suggest that on B6.Tlaa thymocytes, all the conventional TL antigenic specificities (TL. 1,2,3,5,6) as well as the specificities defined by the monoclonal anti-TL antibodies (TL.m2,m3) are carried by a single molecular species.
Polyclonal B cell activation and autoimmunity in New Zealand mice. I. Natural thymocytotoxic autoantibody (NTA).
Authors: Hirose S , Maruyama N , Ohta K , Shirai T
Published: December 2022

The present genetic studies were designed to investigate a possible correlation of spontaneous polyclonal activation of B cells with the spontaneous production of natural thymocytotoxic autoantibody (NTA) in female (NZB X NZW)F1 X NZW backcross mice. We analyzed the spontaneous polyclonal activation of B cells by determining the serum level of naturally occurring anti-hapten (dinitrophenyl, DNP) IgM antibodies. Based on comparisons of the magnitude of the serum DNP binding activities among NZB, NZW, the F1, and the backcrosses to NZW mice, we found that the abnormal polyclonal activation of B cells depends largely on the contribution of NZB genomes. Similar observations were made on serum IgM levels in these mice, and there were made on serum IgM levels in these mice, and there was a highly significant correlation between these two measures in the backcross mice. Despite striking similarities in several observations between NTA and the anti-DNP antibodies, as well as the serum IgM level, there was no significant correlation between the spontaneous production of NTA and the abnormal levels of the anti-DNP antibodies and serum IgM in the backcross mice in both quantitative and qualitative analyses. We also found no significant association between these polyclonal activation of B cells and H-2 complex.
Effect of serum from mice with dormant Friend leukemia viral infections on synthesis and modulation of erythroleukemia cell surface gp70.
Authors: Callahan R M , Marx P A , Marum W G , Wheelock E F
Published: December 2022

Serum of mice with dormant Friend virus infections modulates the expression of cell surface antigens on Friend virus-transformed cells (FLC-745 cells). By radioimmunoassay, the modulated antigen was identified as virion gp70 of Friend leukemia virus. After two days of culture in medium containing 5% serum from mice with dormant Friend virus infections, the modulated cells expressed about 50% less surface gp70 than non-modulated cells cultured in 5% normal mouse serum. After 9 days in culture, the modulated cells expressed no surface gp70; however, these cells contained the same amount of internal gp70 as nonmodulated cells, indicating that gp70 was synthesized during the modulation period. Both modulated and nonmodulated cells grew equally well during the 9 days of culture. These results indicate that the effects of modulation of Friend virus-coded cell surface antigens are restricted to the cell surface.
Immunologic basis of resistance to RL male 1 induced by immunoselected Thy-1.2 negative variants.
Authors: Buxbaum J N , Basch R S
Published: December 2022

Variant cell lines that have lost the Thy-1 antigen have a reduced capacity to induce tumors in syngeneic recipients when compared to Thy-1 positive clones. The negative variants are cloned, cultured cells obtained from the Thy-1.2(theta) positive BALB/c lymphoma RL male 1 in a single-step immunoselection procedure. The reduction appears to be related to an alteration in the host response to the tumor, since both the variant and parental cells induce tumors equally well in irradiated mice. Males are much more susceptible to the inoculated tumor cells, suggesting that the relevant response is restricted to females. A majority of female animals that survive challenge with the variant do not allow growth of the parental tumor when they are injected with a quantity of cells that is uniformly fatal in untreated recipients. Most of the surviving females have an antibody in their sera that is cytotoxic for the variant, its parent, and normal thymocytes. None of the few surviving males had significant titers of the antibody. Cell-mediated immunity directed toward the positive and negative tumor cells was demonstrable in half the surviving animals of both sexes.
Age-dependency of lymphocyte ecto-5'-nucleotidase activity.
Authors: Boss G R , Thompson L F , Spiegelberg H L , Pichler W J , Seegmiller J E
Published: December 2022

The activity of lymphocyte ecto-5'-nucleotidase (ecto-5'-NT) decreases with advancing age, T lymphocyte ecto-5'-NT activity begins to fall after the age of 40 and subjects in the 41 to 50, 51 to 60, 61 to 75, and 75 to 85 age ranges of life have 57, 52, 38, and 19%, respectively, of the T lymphocyte ecto-5'-NT activity of subjects under the age of 40. TG cells (suppressor cells) have 39% of the ecto-5'-NT activity of Tnon-G cells (helper cells) but the increase in numbers of TG cells that occurs with age explains only about 14% of the age-related fall in T lymphocyte ecto-5'-NT activity. B lymphocyte ecto-5'-NT activity remains stable until age 60 and subjects over 60 years of age have 42% of the B lymphocyte ecto-5'-NT activity of subjects under age 60.
Membrane structure-function relationships in cell-mediated cytolysis. I. Effect of exogenously incorporated fatty acids on effector cell function in cell-mediated cytolysis.
Authors: Gill R , Clark W
Published: December 2022

The fatty acid composition of the membrane phospholipids of CTL memory cells restimulated with Con A can be altered significantly when selected exogenous fatty acids are present during the restimulation culture period. Such alterations also lead to significant changes in the subsequent cytolytic capacity of the regenerated CTL. Unsaturated fatty acids increase cytotoxicity, whereas saturated fatty acids lead to decreased cytotoxic function. The kinetics of the fatty acid effect on CTL function is the same as the kinetics of fatty acid incorporation into membrane phospholipids, suggesting that alteration of cytotoxicity results from altering membrane phospholipid fatty acid composition. The initial studies reported here suggest that this effect is mediated at the level of individual CTL, rather than through an alteration of CTL frequency in effector cell populations. Moreover, it seems unlikely that the fatty acids mediate their effect by altering membrane fluidity.
Larger oligomers of IgE are more effective than dimers in stimulating rat basophilic leukemia cells.
Authors: Fewtrell C , Metzger H
Published: December 2022

The relative activity of rat IgE oligomers in eliciting secretion from mast cells and tumor basophils was examined using stable oligomers prepared by cross-linking IgE with dimethyl suberimidate. Oligomers were tested in vivo using passive cutaneous anaphylaxis (PCA) and in vitro by measuring their capacity to induce histamine release from normal rat mast cells and [3H]-5-hydroxytryptamine release from rat basophilic leukemia (RBL) cells. The PCA results confirmed previous work that showed no large differences in the activity of dimers, trimers, and higher oligomers of IgE. The same was also true with normal rat mast cells; however, the RBL cells sharply discriminated between the variously sized oligomers. The stimulatory activity of all oligomers on the RBL cells was enhanced by D2O. The findings imply that the manner by which the clustering of the receptors for IgE leads to generation of signals in RBL cells involves a mechanism capable of discriminating between a variety of polymeric states of the receptors. In addition, our results suggest that no more than a few hundred trimers or an even smaller number of higher oligomers are capable of inducing a considerable amount of secretion from these cells.
Suppressive activity of splenic adherent cells from Plasmodium chabaudi-infected mice.
Authors: Corrêa M , Narayanan P R , Miller H C
Published: December 2022

The immune response of splenic cells to SRBC and LPS or Con A mitogens is suppressed in P. chabaudi-infected mice. When mixed with cells from normal donors, spleen cells from infected mice also suppressed anti-SRBC and mitogenic responses. Suppression was not detected in lymph node cells, bone marrow, or thymocytes from infected mice. Removal of infected red cells had no effect on suppression. The cell population responsible for the suppressive activity was adherent to plastic, resistant to irradiation and anti-Thy-1 plus complement treatment.
The induction of tolerance to DNFB contact sensitivity by using hapten-modified lymphoid cells. III. Effects of hapten concentration on the ability of MLS-disparate cells to induce rapid unresponsiveness.
Authors: Conlon P J , Miller S D , Claman H N
Published: December 2022

We investigated genetic restrictions in the induction of immediate tolerance to DNFB contact sensitivity in mice. Using spleen cells from various donor strains haptenated at 500 micro M DNFB, we were unable to detect any restrictions in tolerance induction in recipients that were either syngeneic or allogeneic to the donor strain. However, if the concentration of hapten used in the in vitro labeling was decreased (from 500 micro M to 2.5 to 5 micro M DNFB), differences in tolerogenesis between the various donor strain haplotypes were found. Haptenated spleen cells labeled with 5 micro M DNFB produced a profound level of unresponsiveness in allogeneic recipients but produced minimal tolerance in syngeneic animals. This tolerant state was shown to be antigen-specific and was not produced by unmodified allogeneic cells alone. Further genetic analysis demonstrated that an efficient tolerant state was produced when the donor of the tolerogen and recipient differed at the MLS locus rather than at either the MHC or minor regions. This phenomenon required viable, Thy 1-bearing cells in the haptenated donor population for efficient tolerogenesis to DNFB contact sensitivity.
Potentiation of the reaginic (IgE) antibody response to ovalbumin in the guinea pig with a soluble metabolic product from Ascaris suum.
Authors: Stromberg B E
Published: December 2022

A soluble antigen, the ACF antigen, obtained from cultures of larvae of Ascaris suum was able to potentiate the reaginic response to an unrelated antigen was administered at the same time or 4 days after ovalbumin, there was a weak primary response and a strong statistically significant secondary IgE response, compared with animals immunized only with ovalbumin. This potentiated response was not observed when the ACF antigen was presented 10 days before or 8 or 12 days after the ovalbumin.
Augmentation of macrophage complement receptor function in vitro. II. Characterization of the effects of a unique lymphokine upon the phagocytic capabilities of macrophages.
Authors: Griffin F M , Griffin J A
Published: December 2022

The means by which a unique lymphokine imparts to macrophages the capacity to ingest complement- (C) coated particles was explored. In contrast to other previously described lymphokines that influence macrophage behavior, the T cell product that enhances macrophage C receptor function was found to act immediately upon contact with macrophages and to be of substantially lower apparent m.w. than either MIF, MAF, lymphotoxin, or interferon. Evidence is presented that indicates that the lymphokine does not act by causing a generalized increase in plasma membrane phagocytic activity or by enhancing phagocytosis mediated by other immunologic receptors. Nor does the lymphokine act by inducing the synthesis of new protein receptors. Our findings suggest that the more likely possibilities by which the lymphokine acts include induction of an increased rate of insertion of C receptors into the macrophage plasma membrane, induction of a rearrangement of C receptors within the macrophage plasma membrane, or a qualitative alteration of the function of existing macrophage C receptors in their relationship with the intracellular machinery involved in phagocytosis.
In vitro synthesis of IgM rheumatoid factor by lymphocytes from healthy adults.
Authors: Koopman W J , Schrohenloher R E
Published: December 2022

Peripheral blood mononuclear leukocytes (MNL) from 22 healthy adults were tested for their capacity to produce IgM rheumatoid factor (RF) in vitro in the presence and absence of pokeweed mitogen (PWM). In no instance was spontaneous elaboration of IgM RF observed. However, stimulation of MNL with PWM resulted in the induction of IgM RF synthesis in 10 out of 22 individuals. The IgM RF in these culture fluids constituted only a small fraction of the total IgM (mean +/- 1 S.D. = 1.01 +/- 1.08%). The lack of correlation of IgM RF with total IgM in these culture fluids argued against nonspecific absorption of non-RF IgM on the IgG substrate utilized in the assay. Furthermore, fraction of supernatants containing IgM RF on Sephadex G-200 indicated the material to co-elute with polymeric IgM and to preferentially bind to Fc coated tubes as opposed to Fab or BSA-coated assay tubes. IgM RF production induced by PWM was dependent upon de novo protein synthesis and exhibited T cell dependence. The data indicate that B cells capable of synthesizing RF commonly occur in normal individuals but are not ordinarily activated.
Antigenic profile of murine natural killer cells.
Authors: Koo G C , Jacobson J B , Hammerling G J , Hammerling U
Published: December 2022

We have determined the antigenic profile of natural killer (NK) cells from C57BL/6 mice that have lytic activity to RLmale1 tumor cells, in a 5-hr 51Cr release assay. To perform the antigenic typing more effectively, we enriched the NK populations by using discontinous BSA density gradient and established a correlation between NK activity and NK-1 antigen in each layer. As NK activity and Nk-1 antigen are both criteria for measuring NK cells, we determined the antigenic profile of NK cells by monitoring both the change in NK activity and NK-1 cells, after elimination of cells with various antisera to lymphocytic alloantigens. We have found that all NK cells expressed Nk-1, Qa-4, and Qa-5 antigens; about 50% of NK cells expressed Thy-1 and Qa-2 antigens, and 25% of NK cells also expressed Lyt-1 antigen. NK cells did not express significant amounts of Qa-1, Qa-3, Lyt-2, and Lyb-2 antigens. Therefore, spontaneous NK cells are heterogeneous with regard to their surface antigens, some of which are T cell antigens. However, the present antigenic profile does not allow us to classify NK cells in the conventional T cells lineage.
Immunologic studies of aging. V. Impaired proliferation of PHA responsive human lymphocytes in culture.
Authors: Hefton J M , Darlington G J , Casazza B A , Weksler M E
Published: December 2022

The impaired response to mitogens of lymphocytes from old persons has been shown to result from the presence of fewer responsive cells and the failure of these cells to divide normally after stimulation. We present additional evidence that the successive divisions of mitogen-responsive lymphocytes from old people are impaired. We labeled sister chromatids with BrdU and identified cells that were dividing for the first, second, or third time in culture. This analysis showed that lymphocyte cultures from old people contained only one-half the number of lymphocytes dividing for a second time and less than one-quarter the number of cells dividing for a third time compared with lymphocyte cultures from young people. It was shown that these changes reflected an absolute decrease in the number of second and third generation cells in cultures from old persons. No alterations in the cytokinetics of proliferation by lymphocytes from old people were found. These results provide additional evidence that mitogen-responsive lymphocytes from healthy elderly people do not undergo as many divisions in cultures with PHA as do lymphocytes from young persons.
Immunoglobulin secretion by mouse X human hybridomas: an approach for the production of anti-idiotype reagents useful in monitoring patients with B cell lymphoma.
Authors: Brown S , Dilley J , Levy R
Published: December 2022

Tumor cells were obtained from a patient with nodular lymphoma, a monoclonal B cell malignancy. These non-Ig-secreting lymphoma cells were hybridized to mouse myeloma cells. Hybridomas secreting human Ig were obtained in high frequency. One clone, which was a stable producer of human heavy and light chains, but which had lost production of mouse light chains, was chosen for study. It secreted a human IgM pentamer. The Ig produced by this clone was purified and used as an immunogen for the production of anti-idiotype antibodies. These antibodies recognized the specific cell surface Ig of the lymphoma cells and have been used to detect idiotype-bearing cells in the blood of the original patient, even at times when the disease was in clinical remission. Moreover, free idiotype could be detected in the patient's serum. Both the levels of Id+ cells and free idiotype correlated with disease activity, rising in relapse and falling in remission.
Role of T lymphocytes in the response to TNP-AECM-Ficoll.
Authors: Mond J J , Mongini P K , Sieckmann D , Paul W E
Published: December 2022

The T cell dependence of the in vivo and in vitro immune response to TNP-Ficoll was re-examined. It was found that after extensive T cell depletion, the in vitro response to TNP-Ficoll was significantly reduced and could be restored with T cells. Despite the apparent T cell dependence, TNP-Ficoll was able to elicit responses by congenitally athymic BALB/c mice in vivo and by spleen cells from these mice in vitro. The in vitro response of normal spleen cells to TNP-Brucella abortus was occasionally diminished as a result of T cell depletion but never as drastically as the response to TNP-Ficoll. This difference in requirement for T cell influence correlates well with our prior classification of these antigens into TI-1 and TI-2 categories.
Control of complement synthesis and secretion in bronchoalveolar and peritoneal macrophages.
Authors: Cole F S , Matthews W J , Marino J T , Gash D J , Colten H R
Published: December 2022

The effect of inflammation on C (C2 and C4) biosynthesis by bronchoalveolar and peritoneal cells was studied with methods that detect changes in synthesis rates and qualitative changes in cell populations. Adherent bronchoalveolar macrophages produced less C2 and C4 than adherent peritoneal macrophages. However, the subset of cells capable of producing C was more than 20-fold greater in the peritoneal cell population than in the population of bronchoalveolar cells. The rate of synthesis per C producing bronchoalveolar macrophage was 5 to 10 times the rate by C producing peritoneal macrophages. In contrast, the effect of an inflammatory stimulus on C production was the result of a change in rate of synthesis per cell, not a change in the proportion of C producing cells. This stimulatory effect was exerted locally, not on a cell population harvested from a distant site. At least two mechanisms for local control of C levels in tissues have been identified--that is, a change in synthesis rate and a qualitative change in macrophage cell population. The capacity to alter C levels at a site of inflammation may be important for C dependent functions in host defenses.
Differential activation of primary and memory "B" lymphocytes.
Authors: Rennick D M , Morrow P R , Leung C Y , Scibienski R J , Benjamini E
Published: December 2022

Immunization of certain strains of mice with the tobacco mosaic virus protein (TMVP) elicits antibodies capable of binding with a decapeptide representing residues 103-112 of TMVP. However, immunization of mice with decapeptide conjugated to a variety of carriers failed to elicit antibodies to the decapeptide in spite of the fact that antibodies were induced to the carriers or to nonrelated peptides similarily conjugated to the carriers. In contrast to the conjugates inability to induce a primary anti-decapeptide response, the conjugates were able to elicit a secondary anti-decapeptide response. Thus, when irradiated mice were transplanted with syngeneic TMVP-primed B cells and carrier-primed T cells, secondary challenge with the decapeptide on the carrier elicited an excellent secondary anti-decapeptide response. Furthermore, the titer and specificity of the antibodies so induced were the same as that induced by secondary challenge with TMVP. These results suggest a difference between primary and memory B cells in their requirements for activation.
An in vitro line of the B cell tumor BCL1 can be activated by LPS to secrete IgM1.
Authors: Gronowicz E S , Doss C A , Howard F D , Morrison D C , Strober S
Published: December 2022

An in vitro line of the B cell tumor BCL1 was developed. The cell line carried u-, S-, and A-chains on the cell surface as judged by analysis of surface iodinated proteins but did not secret Ig. ASfter stimulation with LPS, limpid A, or bacterial lipoprotein, 20 to 40% of the tumor cells matured to IgM secretors when detected in a plaque assay. Two other polyclonal B cell activators, namely dextransulphate and PPD, had at most a marginal stimulatory effect. The ability of the cells to become activated to IgM secretion as well as the expression of cell surface IgM and IgD makes the BCL1 unique among murine B cell tumors.
Memory of Epstein-Barr virus-specific cytotoxic T cells in normal seropostive adults as revealed by an in vitro restimulation method.
Authors: Tanaka Y , Sugamura K , Hinuma Y , Sato H , Okochi K
Published: December 2022

Peripheral blood lymphocytes (PBL) from healthy adults responded with proliferation when stimulated in vitro with lymphoblastoid cell lines (LCL) transformed by Epstein-Barr virus (EBV). Proliferation was not dependent on EBV-serologic status of the PBL donors. After 4 times stimulation with the autologous LCL, viable cells recovered from the cultures consisted mainly of T cells in both EBV-seropositive and seronegative individuals. However, the effector functions of T cells from these 2 groups differed. The effector cells generated from PBL of the seropositive group were cytotoxic to autologous LCL cells, but those from the EBV-seronegative group showed little lysis against autologous LCL cells. These results indicate that the EBV-specific cytotoxic T cells (Tc) can be induced in vitro from seropositive but not seronegative individuals. On the other hand, EBV-nonspecific effector cells detected by K-562 target cell lysis were derived from cultures from both the seropositive and seronegative individuals, especially after the first and second stimulations. Lysis of K-562 targets decreased, however, after the third and fourth restimulation. In 56 effector-target combinations, EBV-specific Tc induced always lysed autologous LCL cells more effectively than allogeneic LCL cells. These data together with HLA-typing results suggested a possibility of the HLA-A or -B restriction of the EBV-specific Tc.
Regulatory role of IgE-binding factors from rat T lymphocytes. III. IgE-specific suppressive factor with IgE-binding activity.
Authors: Hirashima M , Yodoi J , Ishizaka K
Published: December 2022

Incubation with rat IgE of rat mesenteric lymph node cells obtained 8 days after infection with Nippostrongylus brasiliensis (Nb) resulted in the formation of soluble factors with affinity for IgE, i.e., IgE-binding factors(s). The factors were derived from T lymphocytes and were able to suppress an in vitro IgE response without affecting the IgG response. The minimum concentration of rat IgE for the induction of factor formation was 0.3 to 1.0 microgram/ml. Gel filtration of culture filtrates of the IgE-containing culture identified 2 components with IgE-binding activity; one component had a m.w. of between 10,000 and 20,000, and another component had a m.w. of between 25,000 and 50,000. Both factors could be purified by binding to IgE-Sepharose followed by elution at acid pH. Among the two IgE-binding factors, the lower m.w. component had the ability to suppress selectively the IgE response. In contrast to IgE-potentiating factor, which also had affinity for IgE, the IgE-suppressive factor failed to bind to lentil lectin Sepharose. Formation of IgE-specific suppressive factor was not limited to the lymphocytes obtained 8 days after Nb-infection. Incubation with IgE of lymphocytes obtained 4 wk after infection resulted in the formation of both IgE-specific suppressive factor and IgE-potentiating factor, and the activity of the suppressive factor was greater than that of the potentiating factor.
Immune suppression of hematopoiesis in aplastic anemia: activity of T-gamma lymphocytes.
Authors: Bacigalupo A , Podestà M , Mingari M C , Moretta L , Van Lint M T , Marmont A
Published: December 2022

In vitro colony formation (CFU-c) was studied in 7 patients with severe aplastic anemia (SAA) in complete autologous hematologic reconstitution. Colony formation was depressed in all patients (less than 5% of normal). Further studies showed that 1) patients' colony formation could be enhanced by removing T cells from the marrow, but not by removing adherent cells (AC); 2) patients' marrow cells showed a marked CFU-c inhibition against normal allogeneic marrow; 3) CFU-c/suppression could be reduced by removing T cells from the patients' marrow before the co-culture experiments; 4) patients' marrow T cells showed significant CFU-c/inhibition against autologous as well as against allogeneic unrelated normal marrow cells; 5) irradiation with 1500 rads of T cells abrogated their suppressor activity; 6) the latter was found mainly in marrow T cells with IgG receptors (TG+ cells) as well as in the supernatant of marrow T cells cultured overnight; 7) TG+ cells derived from normal donors had no significant CFU-c/inhibitory activity against autologous or allogeneic marrow cells. Active myelosuppression would thus be detectable in patients with SAA in remission and would appear to be mediated by marrow T cells with IgG receptors.
Biochemical characterization of Ia antigens. I. Characterization of the 31K polypeptide associated with I-A subregion Ia antigens.
Authors: Moosic J P , Nilson A , Hämmerling G J , McKean D J
Published: December 2022

Procedures are presented for the preparative isolation of murine Ia antigens directly from splenocyte detergent extracts with monoclonal immunoadsorbents. Utilizing these procedures, three Ia (I-A subregion) polypeptides (alpha, 31K, beta) were isolated and their m.w. and pI values characterized. Evidence is presented that indicates that: 1) the 31K polypeptide probably does not associate with the Ia alpha and beta chain complex during the Ia isolation procedure; 2) the 31K polypeptide is not tightly bound to the alpha/beta Ia complex and can be selectively removed by freezing and thawing and by washing the Ia-immunoadsorbent with buffers containing pyrrolidinone (a polar solvent); and (3) unlike the alpha and beta chains, the 31K polypeptide is not intrinsically radiolabeled with 3H fucose and 3H glucosamine, indicating that the 31K polypeptide either contains a carbohydrate structure that is different from that of the alpha and beta chains or it is not a glycopeptide. These data suggest that although Ia antigens are probably comprised of three polypeptides in the intact cell, only two (alpha and beta) are required to maintain alloantigenic determinants.
Self recognition by autologous mixed lymphocyte reaction-primed cells.
Authors: Tomonari K , Wakisaka A , Aizawa M
Published: December 2022

Human T cells were separated with neuraminidase-treated autologous erythrocytes into auto-rosette-forming cells (ARFC) and non-ARFC (N-ARFC). These 2 subsets were examined for reactivity to autologous non-T cells. When N-ARFC were stimulated by autologous non-T cells, blastogenesis was weak; ARFC, however, proliferated vigorously. ARFC were revealed to be the major subset that responded and proliferated in autologous mixed lymphocyte reaction (AMLR). AMLR-primed cells were restimulated by autologous or allogeneic non-T cells to study self recognition in relation to HLA complex. Self recognition by AMLR-primed cells was closely related to HLA complex, and absolute identity of HLA complex was necessary to recognize allogeneic cells as self. In addition, in respect to the responder cell difference between AMLR and allogeneic MLR, the reactivity of 2 kinds of cells (i.e., AMLR-primed cells and alloreactive cells) strongly suggested that autoreactive T cells were distinguished from alloreactive T cells.
Characterization of a human B lymphocyte-specific antigen.
Authors: Stashenko P , Nadler L M , Hardy R , Schlossman S F
Published: December 2022

A human B lymphocyte-specific antigen (B1) was identified and characterized by the use of a monoclonal antibody. By indirect immunofluorescence, cytotoxicity, and quantitative absorption, B1 was present on approximately 9% of the peripheral blood mononuclear cell fraction and >95% of B cells from blood and lymphoid organs in all individuals tested. Monocytes, resting and activated T cells, null cells, and tumors of T cell and myeloid origin were B1 negative. B1 was distinct from standard B cell phenotypic markers, including Ig and Ia antigen. Removal of the B1 positive population in peripheral blood eliminated all B cells capable or responding to pokeweed mitogen by maturation to Ig-producing cells.
Regulation of immune response in allogeneic mixed spleen cell cultures. I. Influence of I-region on the generation of suppressor cells.
Authors: Kim Y T , Schwartz A , Moody C , Siskind G W , Weksler M E
Published: December 2022

The immune responses of allogeneic mixed spleen cell cultures (MLC) to the T-dependent antigen, SRBC, and to the T-independent antigen, DNP-PAA, were investigated. The immune response to DNP-PAA in MLC with certain strain combinations was always suppressed as compared with the expected PFC response calculated from the PFC responses of the individual strains. This suppression was eliminated by treating the spleen cells with RAMB antiserum plus complement before the incubation of the MLC with DNP-PAA. It can be concluded that the suppression in the PFC response to the T-independent antigen DNP-PAA in MLC is due to the generation of suppressor T-cells. The PFC response to the T-dependent antigen, SRBC, in MLC showed either suppression, no change, or rarely augmenation, suggesting that the allogeneic mixed spleen cell cultures can generate both suppressor and helper T cells and that the balance between helper and suppressor activity regulates the PFC response to a T-dependent antigen. Suppressor activity was also generated in a one-way MLC, but the degree of suppression depended upon which of the two strains was responding. Similar amounts of thymidine were incorporated in the one-way MLR irrespective of which strains was responding. Thus, the extent of proliferation in one-way MLR is not related to the degree of suppressor activity generated. The results further indicate that a difference between two strains in the I-C, S, and G regions of the major histocompatibility complex is required to generate suppressor activitiy that can depress the response to a T-independent antigen, MLC between strains differing in K, I-A, I-B, I-J, I-E, and D regions generate little or no suppressor activity in this system.
High molecular weight surface glycoproteins of murine lymphocytes.
Authors: Hoessli D C , Vassalli P
Published: December 2022

High m.w. glycoproteins in the range of 170 and 210K represent major cell surface components of murine lymphocytes. The expression of such glycoproteins has been characterized for thymocytes and peripheral T and B lymphocytes in BALB/c mice using surface and biosynthetic labeling, nonionic detergent extraction, and immunoprecipitation with antibodies directed against antigenic determinants expressed on the cell surface of a murine T cell lymphoma. Immunoprecipitates were then resolved by 1-dimensional and 2-dimensional gel electrophoresis. Two groups of antigenically distinct glycoproteins have been defined: 1) a 170K component present on thymocytes and peripheral T lymphocytes but undetectable on B lymphocytes; this glycoprotein has been termed T 170 to suggest its potential use for distinguishing T from B lymphocytes; 2) a higher m.w. glycoprotein bearing antigenic determinants common to T and B cells but expressed as one 180K glycoprotein on thymocytes, 2 glycoproteins of 180 and 190K on peripheral T lymphocytes, and as one 210K glycoprotein on B lymphocytes. The relationships of these glycoproteins with the other known lymphocyte surface markers of high m.w. is discussed.
The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs).
Authors: Goetzl E J , Pickett W C
Published: December 2022

The lipoxygenation of arachidonic acid in basophils, mastocytoma cells, and other leukocytes generates the unstable intermediate 5-hydroperoxy-eicostaetraenoic acid, which is converted in part to a series of complex hydroxy-eicosatetraenoic acids (HETEs) with additional polar substituents and 3 conjugated double bonds. One of the products, 5,12-di-HETE, is chemotactic for human neutrophils in vitro at a concentration as low as 3 ng/ml and evokes a maximal neutrophil chemotactic response at 30 ng/ml, as compared to 1000 ng/ml for 5-HETE and 10,000 to 20,000 ng/ml for 11-HETE and 12-HETE. In contrast, other products in the same series, such as the slow reacting substance 5-hydroxy-6-glutathionyl-eicosatetraenoic acid (leukotriene C), and the platelet-derived 8,9,12-trihydroxy-eicosatrienoic acid and 8,11,12-trihydroxy-eicosatrienoic acid exhibited only marginal neutrophil chemotactic activity. Only 5,12-di-HETE released significant quantities of beta-glucuronidase and lysozyme from the neutrophils, but the maximal level of enzyme release was far less than that for the chemotactic fragment of C5 and the formyl-methionyl peptides.
Enhanced transfer of experimental allergic encephalomyelitis with strain 13 guinea pig lymph node cells: requirement for culture with specific antigen and allogeneic peritoneal exudate cells.
Authors: Driscoll B F , Kies M W , Alvord E C
Published: December 2022

Previously, we reported that transfer of experimental allergic encephalomyelitis (EAE) with sensitized peritoneal exudate cells (PEC) in strain 13 guinea pigs is markedly enhanced if the cells are first cultured with specific antigen, myelin basic protein (BP). These cells also undergo considerable antigen-specific proliferation. In contrast, the data reported here show that lymph node cells (LNC) from sensitized animals display neither enhanced transfer nor antigen-specific proliferation after culture with BP. Enhanced transfer is obtained, however, if a second nonspecific signal is available. This second signal is provided by the presence of normal allogeneic strain 2 PEC in culture. After culture with BP and strain 2 PEC, 2.5 to 5 x 10(7) strain 13 LNC transfer disease reproducibly, in contrast with approximately 1 x 10(9) previously required for successful transfer. Addition of allogeneic or syngeneic PEC without antigen does not lead to enhanced transfer by LNC. Culture with normal syngeneic PEC plus BP oly infrequently enhances transfer by LNC. The intense mixed lymphocyte reaction (MLR) induced by addition of strain 2 PEC to strain 13 LNC precludes the use of 3H-TdR incorporation for detection of proliferation by EAE effector cells. However, inhibition of transfer with low doses of mitomycin C (2 to 5 micrograms/ml) pluse the fact that EAE effector cells are found almost exclusively in the light fraction of BSA gradients after (but not before) culture suggests that the latter are induced to proliferate in culture.
Inhibition of concanavalin A-induced human lymphocyte mitogenic factor (Interleukin-2) production by suppressor T lymphocytes.
Authors: Northoff H , Carter C , Oppenheim J J
Published: December 2022

Supernatants of fresh human MNL stimulated with concanavalin A (Con A) generally contain little or no lymphocyte-derived mitogenic factor (LMF or Interleukin-2). However, preincubation of MNL in culture medium for 2 to 5 days before stimulation with Con A rendered them capable of producing increasing LMF. The production of LMF by reincubated MNL was inhibited by readdition of autologous fresh MNL or E-rosetting (T) lymphocytes. The producing cells were T lymphocytes; however, the production of LMF was monocyte dependent. LMF eluted from a Sephadex G150 column in 2 peaks at 12 to 27,000 and 50 to 70,000 daltons. Both species of LMF were mitogenic for mouse (C3H/HeJ) thymocytes and for human T and B cells. LMF production was not affected by x-irradiation (less than or equal to 2500 R) before preincubation; it was, however, abolished by the addition of 10(-7) M hydrocortisone during the preincubation period. LMF production by fresh MNL could be moderately enhanced by the addition of cimetidine, a drug that is known to interfere with histamine H2 receptors on suppressor T cells. Presumably, preincubation of MNL reduces the activity of Con A-induced suppressor cells. We conclude that human peripheral blood contains suppressor T cells that when activated by Con A regulate the production of LMF by other T cells in response to Con A.
Immune suppression in vivo with antigen-modified syngeneic cells. V. Interacting T cell subpopulations in the suppressor pathway.
Authors: Sherr D H , Benacerraf B , Dorf M E
Published: December 2022

Intravenous administration of syngeneic C57BL/6 cells coupled with the palmitoyl derivative of the protein antigen fowl gamma-globulin (p-FgG) results in a state of FgG carrier-specific nonresponsiveness, mediated in part by suppressor T cells. At least two populations of cells are involved in generating a suppressor pathway in this system, one induced in recipients of p-FgG coupled cells and the other contributed by normal recipients of cells from suppressed donors. Induction of T cells capable of transferring suppression to normal recipients is sensitive to 1) low doses of cyclophosphamide, 2) adult thymectomy, and 3) in vivo treatment with anti-I-J antisera. This T cell subset bears I-J determinants and is functionally sensitive to irradiation. The induction of the second population required for immune suppression is sensitive to 1) low doses of cyclophosphamide and 2) adult thymectomy. In addition, compatibility of genes at the Igh locus appears not to be essential for cellular interaction between these populations. The evidence that interacting T cell subpopulations are involved in a suppressor pathway induced with protein-modified syngeneic cells is discussed relative to other systems in which T-T cell interactions are postulated.