bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immature B cells as the target for in vivo tolerance induction.
Authors: Klinman N R , Schrater A F , Katz D H 
Published: December 2022

Abstract
In vitro studies have indicated that immature B cells at a specific stage in clonal maturation are exquisitely susceptible to tolerance induction by antigens and antigen concentrations that have no effect on mature B cells. In order to determine if a similar phenomenon obtains for B cells in vivo, mice were tolerized with DNP-D-GL and their splenic and bone marrow B cells were carefully washed and analyzed for responsiveness in the splenic focus system. The results demonstrate that, whereas the treated mice themselves become rapidly unresponsive to either DNP or TNP on a heterologous carrier, a measurable decrease in the frequency of splenic DNP-responsive B cells occurs only very slowly with a half-life of approximately 2 wk and TNP-responsive splenic B cells are only marginally, if at all, affected. A progressive decrease in DNP-responsive bone marrow B cells is also observed and occurs at a somewhat more rapid rate than the decrease in splenic B cells. The rate of decrease of splenic precursor cells is totally consistent with the normal attrition of mature B cells in the absence of newly generated DNP-specific B cells. Thus, in vivo tolerance, like in vitro tolerance may only eliminate immature B cells as they emerge from their stem cell pool and has no effect on mature resident B cells. This conclusion is consistent with the additional finding that 1 mo after tolerance induction, the majority of remaining DNP-responsive B cells in the bone marrow is found in very early precursors that have not, as yet, acquired their immunoglobulin receptors. Finally, the exquisite specificity of this tolerance induction would be totally consistent with a physiologic role for a clonal abortion mechanism that could specifically eliminate self-reactive B cells while leaving essentially intact the B cell repertoire responsive to non-self determinants.
In vitro growth of cytotoxic human lymphocytes. III. The preparation of lectin-free T cell growth factor (TCGF) and an analysis of its activity.
Authors: Lotze M T , Rosenberg S A 
Published: December 2022

Abstract
Supernatants containing T cell growth factor (TCGF) that are produced by incubating human peripheral blood lymphocytes with the mitogenic lectin, phytohemagglutinin (PHA) have previously been shown to allow the successful culture of antigen-reactive T cells. The continued presence of PHA in these preparations, however, complicates the analysis of the direct effects of TCGF. In this report we describe in detail methods used to remove greater than 99% of the exogenous mitogen with a 77% yield of TCGF. TCGF activity precipitated between 50 and 75% saturated ammonium sulfate and was freed of 90% of exogenous PHA. Residual PHA was removed by absorption on affinity columns of Sepharose 4B linked to rabbit anti-PHA antibody. Ninety-nine percent of PHA was removed by these techniques based on assays of the mitogenesis of fresh lymphoid cells and the use of tracer quantities of highly purified radiolabeled PHA. This partially purified TCGF (PP-TCGF) supported the continued growth of mitogen or alloactivated lymphoid cells but not fresh resting cells unless high starting numbers of lymphoid cells are used. An increase of up to 500 times the number of specific lytic units/culture was obtained by expanding alloactivated cells in PP-TCGF when compared to the crude TCGF supernatants.
Immune restoration and/or augmentation of local xenogeneic graft versus host reaction by Cimetidine in vitro.
Authors: Mavligit G M , Calvo D B , Patt Y Z , Hersh E M 
Published: December 2022

Abstract
The immunorestorative effect of Cimetidine in vitro on the T cell-induced local GVH reaction in vivo was studied in 43 cancer patients and 43 normal healthy donors. Both low dose (10(-5) M) and high dose (10(-4) M) Cimetidine induced significant, albeit partial, immune restoration among GVHR-negative cancer patients (p less than 0.05, p less than 0.01, respectively) with the high dose being significantly more effective (p less than 0.05). In contrast, similar Cimetidine doses induced only moderate augmentation (p greater than 0.05) among GVHR-positive cancer patients and a marginal one among normal healthy donors. In the latter 2 groups, Cimetidine was found to be occasionally detrimental in that it induced a conversion from a positive to a negative GVH reaction. These results support the concept of anti-suppressor cell activity ascribed to Cimetidine. However, the possibility of a detrimental effect should be born in mind in planning future clinical trials. We propose that the use of Cimetidine be limited to cancer patients with documented increase in suppressor cell activity associated with defective T cell function under close serial monitoring.
Genes of the H-2 complex regulate the antibody response to murine leukemia virus.
Authors: Vlug A , Schoenmakers H J , Melief C J 
Published: December 2022

Abstract
The influence of the major histocompatibility complex of the mouse (H-2 complex) on the antibody response against murine leukemia virus (MuLV) was investigated after 3 different ways of virus presentation (milk transmission of virus, spontaneous virus activation, and immunization with inactivated virus). The antibody response against MuLV was measured in the sera of H-2 congenic C57BL V+ sublines (V+ denotes positive for milk-transmitted MuLV), (B10.AV+ X C57BL)F1 mice, (C57BL X AKR)F1 mice and of C57BL animals after immunization with inactivated AKR virus. The pattern of immune responsiveness of the different C57BL strains to MuLV was independent of virus replication and was similar for the 3 ways of virus presentation. Serum antibody levels were controlled by 2 genes within the H-2 complex. The first gene (Ir-MuLV-1) was located in the I-A region and was complemented by a second gene (Ir-MuLV-2), which was situated in the regions to the right of the I-B region. Presence of 2 responder alleles (Ir-MuLV-1+,2+) led to an optimal antibody response (H-2b haplotype). Animals that only expressed a responder allele in the I-A region (Ir-MuLV-1+,2-) were intermediate responders. Animals lacking a responder allele in the I-A region (Ir-MuLV-1-,2+ or Ir-MuLV-1-,2-) were low responders.
The third component of complement: covalent attachment of a radioactive sugar to the labile binding site of C3 via the alternative pathway.
Authors: Mann J , O'Brien R , Hostetter M K , Alper C A , Rosen F S , Babior B M 
Published: December 2022

Abstract
A complement- (C) fixing particle consisting of agarose beads to which 5-thioglucose was attached by a --S--S-- bond (agarose-thioglucose) was employed to investigate the mechanism of attachment of C3 to surfaces. When whole serum containing [125I] C3 was incubated with agarose-thioglucose, labeled C3b was taken up in a form that was not removed by 2 M NaCl but was released by 10 mM dithiothreitol. Deposition of DTT-releasable C3b was dependent upon the alternative pathway of C activation. Gel electrophoresis of DTT-releasable C3b from similar experiments performed with unlabeled serum and agarose-[3H]thioglucose showed that the liberated C3b contained a molecule of radioactive thioglucose attached to the alpha'-chain by a covalent bond that was stable to mercaptoethanol. We propose that the thioglucose-alpha' chain bond was formed during the course of C activation by a reaction between the "labile binding site" of newly released C3b and the (then) particle-bound sugar. This formulation implies that the reaction by which C3b attaches to 5-thioglucose in this system is the reaction responsible for opsonization by C3b, and that the C3b-linked sugar represents a marker for the labile binding site. Incubation of the particle-bound C3b in serum resulted in the cleavage of the covalently linked alpha'-chain to several smaller polypeptides, the major cleavage product having a m.w. of 70,000.
T cell subpopulations required for the human cytotoxic T lymphocyte response to influenza virus: evidence for T cell help.
Authors: Biddison W E , Sharrow S O , Shearer G M 
Published: December 2022

Abstract
The requirement for specific T cell subsets in the in vitro generation of human influenza virus-immune cytotoxic T lymphocyte (CTL) responses was investigated. Peripheral blood T cell populations were identified by and selected for their reactivity with the monoclonal antibodies OKT3, OKT4, and OKT8. Influenza virus-immune CTL effectors are OKT3+, OKT4-, and OKT8+. Analysis of CTL precursors demonstrates that: 1) influenza-immune CTL precursors are OKT3+, OKT4-, and OKT8+; 2) CTL precursors require radioresistant OKT3+ helper T cells in order to generate strong cytotoxic responses; and 3) helper T cells can be obtained from either the OKT4+ or OKT4- populations, but more potent help was generated by the OKT4+ subset. The demonstration of a helper T cell requirement for the generation of influenza virus-immune CTL suggests that helper T cells may be involved in the previously documented HLA-linked Ir gene control of influenza-immune CTL responsiveness.
Regulation of antigen-induced lymphoproliferation by BSA gradient-separated T cell fractions.
Authors: Emmons R P , Carvalho E M , Horwitz D A 
Published: December 2022

Abstract
Human T cells from 6 volunteers immunized with keyhole limpet hemocyanin (KLH) or tetanus toxoid were fractionated on bovine serum albumin (BSA) gradients. These T cell fractions were then recombined with autologous unseparated mononuclear cells or unseparated T cells to determine the effect of each fraction on the proliferative (DNA synthetic) response to the immunizing antigen. Using this separation technique, we were able to define 2 fractions of T cells of widely different densities that had a suppressive effect on the proliferative response to KLH of unfractionated T cells. The demonstration of suppressive activity was possible only if cells were tested within 8 wk of immunization with KLH. These suppressive T cell fractions differed not only in density but also in surface characteristics. Fraction 1 cells had a high proportion of Ia+ cells but no Fc receptors for IgG (FcRG-) were seen, whereas cells from fraction 4 (of higher density) were Ia- and were composed of 12.1 +/- 1.2% FcRG+ cells. this suppression was shown to be specific for the immunizing antigen. One individual who had been immunized with KLH for more than 1 yr in which suppression of KLH-induced proliferation was no longer demonstrable was given primary immunization to tetanus toxoid. Suppression could be demonstrated in fractions 1 and 4 specific for tetanus toxoid; there was no demonstrable effect of these T cell fractions on the response to KLH. We postulate that these are different functional populations of suppressor T cells that regulate antigen specific lymphoproliferation.
Activation of antigen-specific suppressor cells in human schistosomiasis mansoni by fractions of soluble egg antigens nonadherent to Con A sepharose.
Authors: Rocklin R E , Tracy J W , El Kholy A 
Published: December 2022

Abstract
The nature of the mononuclear suppressor cell and the fraction of crude soluble egg antigen (SEA) capable of activating antigen-specific suppressor cells were studied in 32 Egyptian children infected with schistosomiasis mansoni. Crude SEA was fractionated on Con A Sepharose, and the unbound and bound material (eluted with alpha-methyl-D-mannoside) was recovered for use in the generation of suppressor cells by the use of a co-culture technique. The glycoprotein fraction was further purified by DEAE cellulose chromatography to isolate the major serologic antigen (MSA-1). We found that both the crude SEA and the "protein" fraction (nonadherent to Con A Sepharose) of SEA was capable of inducing antigen-specific suppressor cell activity in a dose-dependent manner. The glycoprotein fraction of SEA (including MSA-1) was responsible for inducing nonspecific suppression. The antigen-specific suppressor cell was characterized in terms of its adherence properties of plastic and the presence of a receptor for sheep erythrocytes (E). The nonadherent, E-rosette-positive mononuclear cells were found to be activated by the crude SEA, and the "protein" fraction of SEA was found to exert an antigen-specific suppressor influence. Clinically, suppressor cell activity was found to be statistically greater in patients with a high intensity of infection compared to those with a low intensity of infection, but it was not different in patients with regard to the presence or absence of organomegaly. These results provide further information on one of the immunoregulatory mechanisms operative in human S. mansoni infection and on the nature of the antigen(s) that activates this response during the course of infection.
Monomorphic anti-HLA-A,B,C monoclonal antibodies detecting molecular subunits and combinatorial determinants.
Authors: Brodsky F M , Parham P 
Published: December 2022

Abstract
Thirteen monoclonal antibodies that react with monomorphic determinants on the HLA-A,B,C-beta 2-microglobulin (beta 2m) molecule were characterized. Analysis of antibody activity included inhibition by papain-solubilized HLA antigens and free beta 2m, antibody binding to mouse-human somatic cell hybrids containing human chromosome 6 or 15, and antibody cross-reactivity with lymphocytes from nonhuman species. Two criteria for monomorphism were established: 1) equal inhibition or absorption of antibody activity by all papain-solubilized HLA antigens or cell lines of different HLA specificities tested; and 2) nonpolymorphic cross-reactivity within another species or subspecies. On the basis of soluble antigen inhibition and binding to somatic cell hybrids, 3 classes of antibodies were detected: anti-beta 2m, anti-heavy chain, and anti-complex (against a combinatorial determinant formed by heavy chain and beta 2m). Antibody cross-reaction patterns in nonhuman species were suggestive that these monomorphic antibodies detect a limited number of determinants, minimally one on each chain and 2 combinatorial determinants. Examination of the known primary sequences for HLA-A2, HLA-B7, H-2Kb, and mouse, rabbit and human beta 2m provides a molecular explanation for this limited mouse anti-HLA monomorphic antibody activity.
Hapten-coupled monoclonal anti-I-A antibodies provide a first signal for the induction of suppression.
Authors: Bromberg J S , Nepom J T , Benacerraf B , Greene M I 
Published: December 2022

Abstract
A mechanism for induction of hapten-specific immune unresponsiveness is described that utilizes a hapten-conjugated monoclonal anti-Ia antibody to direct the in vivo immune response. Azobenzenearsonate- (ABA) coupled anti-I-Ak antibodies provide a potent first signal for the induction of nonresponsiveness to ABA in H-2k,a mice. The use of an anti-Ia antibody requires haplotype matching and may selectively direct the hapten signal, because other haptenated monoclonal antibodies are ineffective. There is an absolute requirement for a second signal to achieve in vivo suppression; the signal may be substituted by the generation of an allogeneic effect at the time of hapten presentation. We suggest that these methods allow for specific targeting of hapten-suppressive signals that differ considerably from other model systems of tolerance to haptenated immunoglobulins. The results are discussed in relation to a potential role for an Ia+ cell involved in the induction of regulating suppressor pathways.
Normal and malignant human myelocytic and monocytic cells identified by monoclonal antibodies.
Authors: Bernstein I D , Andrews R G , Cohen S F , McMaster B E 
Published: December 2022

Abstract
Two cytotoxic IgM monoclonal antibodies reactive with human cells of myeloid origin are described. Each antibody was tested for reactivity with normal and malignant cells of myeloid origin by using immunofluorescent and cytotoxic assays. Antibody 5F1 defines a determinant expressed by peripheral blood monocytes and platelets. Antibody 1G10 detects a determinant expressed in high concentration on granulocytes and in low concentration on a subset of monocytes. Neither antibody reacts with peripheral blood lymphocytes, erythrocytes, or thymocytes. In bone marrow, 5F1 stains monocytic and nucleated erythrocytic cells, whereas 1G10 stains cells of the granulocytic lineage. Each antibody also reacts with subsets of acute nonlymphocytic leukemia cells. These reagents should be useful in delineating stages of normal and malignant myeloid differentiation.
Anti-f Met-Leu-Phe: similarities in fine specificity with the formyl peptide chemotaxis receptor of the neutrophil.
Authors: Marasco W A , Showell H J , Freer R J , Becker E L 
Published: December 2022

Abstract
We have prepared antisera in both rabbits and rats against f Met-Leu-Phe conjugated to a variety of carrier proteins. Over 40 peptides with widely varying reactivity for the neutrophil formylpeptide receptor have been tested for their ability to bind to rabbit antibody raised against fMLP10-BSA. Structure-activity studies of peptides structurally related to f Met-Leu-Phe demonstrate that the N-formyl group is mandatory for maximum antibody binding activity. Methionine in position 1 and phenylalanine in position 3 are found to confer maximum binding activity. Stereoselectivity of the antibody-combining site also has been demonstrated. Comparison of the ability of the peptides to bind to the antibody receptor with their reactivity for the neutrophil has demonstrated a strong correlation in the rank order of reactivity of the numerous synthetic peptides: for the alpha NH2-acyl group, r = 0.94; for position 1, r = 0.90; for position 2, r = 0.97; and for position 3, r = 0.78. This strong correlation is seen across species lines with both rabbit and rat antibodies. Significant differences, however, in the specificity of the antibody and neutrophil receptors are seen at the carboxyl terminus of phenylalanine, and beyond the phenylalanine ring, r = 0.29. In addition, bacterial chemotactic factor-enriched butanol extracts from Escherichia coli culture filtrates can also bind to anti-f Met-Leu-Phe, affording additional evidence for the similarity in the structure of the bacterial chemotactic factor to the synthetic chemotactic peptides.
Inhibition of human natural killer cell activity by cytophilic immunoglobulin G.
Authors: Sulica A , Gherman M , Galatiuc C , Manciulea M , Herberman R B 
Published: December 2022

Abstract
The natural killer (NK) cell activity of human peripheral blood mononuclear cells (PBL) was found to be increased after incubation at 37 degrees C for 2 hr. The observed increase was shown to be associated with release from inhibition by human serum factors, because incubation in autologous serum interfered with augmentation. The serum-mediated effect appeared attributable to the degree of binding of labile IgG to PBL and could be reduced by selective depletion of IgG from the serum. Human monomeric IgG was found to efficiently inhibit the culture-induced augmentation of NK activity; the inhibitory IgG had properties consistent with those described for cytophilic IgG and was mediated through the Fc region of IgG. The inhibition by monomeric IgG occurred at 0 degrees C as well as at 37 degrees C and this could be induced even after culture-induced augmentation of NK activity. Thus, binding of monomeric IgG to human PBL appears to reversibly inhibit their NK activity. These results provide evidence for a novel mechanism for negative regulation of NK activity.
The production of plasminogen activator by afferent but not efferent lymph cells emigrating from chronic granulomatous lesions in sheep.
Authors: Wasi S , Vadas P , Chin G W , Movat H Z , Hay J B 
Published: December 2022

Abstract
Subcutaneous granulomas were induced in sheep by injecting Freund's adjuvant. At varying times thereafter afferent and efferent lymphatics draining the granulomas were cannulated. Lymph was collected for periods up to several days or weeks from either normal skin or from inflammatory lesions 15 to 120 days after the initiation of the lesions. The fibrinolytic activity of cells and cell culture medium in which cells were grown was assayed by using 125I-fibrin plates. No detectable enzyme activity was found from normal afferent, normal efferent, or stimulated efferent lymph cells. Afferent granuloma cells produced a plasminogen-dependent, DFP inhibitable protease activity that was dependent on the cell concentration and the incubation time. Results of cell separation techniques such as sedimentation velocity, adherence on fibrin plates, and Sephadex G-10 fractionation showed that the large, macrophage-like cell population in afferent lymph was secreting the plasminogen activator. The lymph cells collected from lesions 1 to 2-mo-old were more active than an equivalent number of cells collected from earlier or later lesions. When tuberculin was injected directly into lesions the lymph cells that appeared in the subsequent 1 to 2 days produced more enzyme per cell. The relationship between plasminogen activator and other possible mediators that appear in either the cells or plasma of afferent lymph is discussed.
Streptococcal group A carbohydrate has properties of both a thymus-independent (TI-2) and a thymus-dependent antigen.
Authors: Briles D E , Nahm M , Marion T N , Perlmutter R M , Davie J M 
Published: December 2022

Abstract
Streptococcal group A carbohydrate, which elicits mouse antibody of primarily the IgM and IgG3 isotypes, is relatively nonimmunogenic in nu/nu or xid mice, and thus appears to be a type of TD-2 antigen. The TD-2 antigens described previously have been proteins that elicit IgG antibody primarily of the IgG1 and IgG2 isotypes. Our findings indicate that TD-2 properties may also be a characteristic of at least some carbohydrate antigens that can elicit IgG antibody predominantly of the IgG3 class.
A role for C-reactive protein in the complement-mediated stimulation of human neutrophils by type 27 Streptococcus pneumoniae.
Authors: Edwards K M , Gewurz H , Lint T F , Mold C 
Published: December 2022

Abstract
Although C-reactive protein (CRP) has been shown to be opsonic when bound to erythrocytes, its role in bacterial phagocytosis is unclear. Chemiluminescence (CL), a measure of the metabolic stimulation of neutrophils, was used to investigate the effects of CRP and complement (C) on the interaction between phagocytes and Streptococcus pneumoniae, type 27 (Pn27). CRP binding to Pn27 was demonstrated by using radiolabeled CRP, and Scatchard analysis indicated a saturation binding of about 10(7) CRP molecules/CFU. When Pn27 was pretreated with normal human serum and added to neutrophils, the CL response observed was directly related to the number of bacteria and the amount of serum added. Although bacteria pretreated with CRP alone produced minimal CL, the addition of CRP to serum resulted in a two to 13-fold enhancement of the CL response. CRP enhancement of CL was not observed with heated serum or serum from a patient genetically lacking C2. CRP bound to Pn27 was found to cause consumption of C3 and C4 in normal human serum, indicating activation of the classical C pathway. Because CRP opsonization might provide early protection in the nonimmune host, we tested the ability of CRP to enhance opsonization in serum with markedly decreased immunoglobulin. CRP enhanced the CL response in serum from a hypogammaglobulinemic patient to between 12 and 16 times the serum control. These studies show CRP binds to Pn27 and in the presence of C enhances the opsonization of these organisms. These findings support the concept that CRP plays a protective role in bacterial infection.