bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of anti-H-2K and H-2D alloantibodies in enhancement and acute antibody-mediated rejection of mouse skin allografts.
Authors: de Waal R M , Capel P J , Koene R A
Published: December 2022

The enhancing and destructive effects of anti-H-2Kd and anti-H-2Dk antibodies were studied in B6AF1 recipients of B10.D2 or B10.BR skin allografts. The anti-H-2 antibodies were isolated from B6AF1 anti-B10.D2 and B6AF1 anti-B10.BR alloantiserum by adsorption to donor strain red blood cells and subsequent elution. Acute antibody-mediated rejection of B10.D2 or B10.BR skin grafts was readily induced by administration of anti-H-2K or H-2D antibodies, respectively, along with rabbit complement. Treatment of the B6AF1 recipients with the antibody eluates on day 0, 2, and 4 after transplantation resulted in specific and significant prolongation of graft survival. Both graft destruction and enhancement can therefore be mediated by antibodies directed against the same H-2 specificity.
Induction of anti-ssDNA antibodies in normal and preautoimmune mice in vivo.
Authors: Pancer L B , Bell D A , Singhal S K
Published: December 2022

Splenic lymphoid cells of normal and preautoimmune mice escape normal regulatory mechanisms in vitro and spontaneously synthesize anti-ssDNA antibody in the absence of any exogenous antigen. In addition, both the cultured cells and their cell-free supernatants were capable of inducing specific anti-ssDNA responses in vivo upon their injection into syngeneic recipients. The response was host-derived, required the participation of B and T cells, and was not due to polyclonal activation. The immunogen responsible for this response appeared to be membrane-associated, was found predominantly on cultured T cells, and was sensitive to DNase and proteolysis.
Role of accessory cells in B cell activation. I. Macrophage presentation of TNP-Ficoll: evidence for macrophage-B cell interaction.
Authors: Boswell H S , Sharrow S O , Singer A
Published: December 2022

The importance of cell interaction for thymic independent antigen responses has not been widely appreciated. The present report demonstrates, however, that macrophage-B cell interaction may be an important feature of B ce-l activation for the response to at least one polysaccharide thymic independent antigen, TNP-Ficoll. Experiments were performed demonstrating that a strict accessory cell requirement exists for the thymic independent response to soluble TNP-Ficoll, and that such accessory cells are both adherent and phagocytic, that is, macrophages. It was further demonstrated that macrophages could be pulsed with TNP-Ficoll and that these pulsed macrophages could activate B cells to respond, but only if the pulsed macrophages were viable. Thus, one function that macrophages can fulfill in responses to TNP-Ficoll is the specific function of antigen presentation. Such presentation of TNP-Ficoll by macrophages to B cells suggests that the antigen may not be activating B cells directly, and raises the possibility that the interaction of B cells and macrophages might be genetically restricted.
Is experimental autoimmune myasthenia gravis induced only by acetylcholine receptors?
Authors: Claudio T R , Raftery M A
Published: December 2022

EAMG has been induced in a wide variety of animals by using AcChR purified from electric organ and muscle sources. Electrophoresis of SDS polyacrylamide gels heavily loaded with purified AcChR often reveals the presence of minor contaminants. To test whether these contaminants or any other components present in Torpedo californica AcChR preparations could induce EAMG, solubilized Torpedo membrane fragments were depleted of AcChR by passage over an alpha-BuTx-conjugated resin and then injected into Lewis rats in an attempt to induce EAMG. The results demonstrated that some of the minor contaminants present in purified AcChR preparations were antigenic, but EAMG could not be induced with preparations enriched in these contaminants or containing other Torpedo non-AcChR components and lacking AcChR. The conclusion drawn from this study was that the acetylcholine receptor was the only component present in Triton X-100-solubilized Torpedo californica membrane fragments that could induce EAMG.
H-2 antigen requirements in the in vitro induction of SV40-specific cytotoxic T lymphocytes.
Authors: Gooding L R , Edwards C B
Published: December 2022

T cytotoxic cells generated to syngeneic SV40 virus transformants lyse only SV40 target cells that are syngeneic at the H-2 locus. In contrast, SV40-specific tumor transplantation immunity shows no requirements for syngeneic H-2. Inoculation of allogeneic or even xenogeneic transformants will confer immunity to a challenge of syngeneic SV40 tumor cells. The experiments described here represent an attempt to reconcile these apparently conflicting observations. In our hands, generation of SV40-specific T cytotoxic cells in vitro requires both in vivo priming and secondary in vitro sensitization. We have found that priming for a secondary syngeneic-restricted response requires only that the cell employed be SV40 transformed. That is, priming may be accomplished with syngeneic, allogeneic, or xenogeneic SV40 transformants. Thus, the apparent lack of H-2 restriction in vivo immunity does not eliminate a role for the H-2-restricted cytotoxic T cell in tumor transplantation immunity.
Antigen-specific factors produced by carrier-primed New Zealand Black mice.
Authors: Sawada S , Dauphinée M J , Talal N
Published: December 2022

We studied antigen-specific suppression in NZB and B/W mice to investigate immunoregulatory circuits associated with autoimmune disease. Young NZB and B/W mice produced ample suppressor factor, and acceptor cells were present even in older mice. A low m.w. antigen-specific enhancing factor capable of augmenting the secondary in vitro IgG antibody response to DNP was found. These results indicate the complexity of immunoregulation in these autoimmune-susceptible mice.
Polyclonal activation of murine B lymphocytes by Fc fragments. I. The requirement for two signals in the generation of the polyclonal antibody response induced by Fc fragments.
Authors: Morgan E L , Weigle W O
Published: December 2022

Fc fragments derived from human IgG1 induce murine splenic B lymphocytes to undergo proliferation and differentiation to antibody-secreting cells. The polyclonal antibody response was found to require both the presence of macrophages and T cells. Spleen cell cultures from nude mice or T cell-depleted normal mice proliferate to the level of untreated control mice but do not produce polyclonal antibody unless T cells are added. Regulation of the Fc fragment induced B cell differentiation to antibody synthesis apparently occurs through two distinct signals. One signal is provided by Fc fragments for proliferation and the other by T cells for differentiation. This suggestion is supported by the observation that spleen cell preparations, devoid of T cells, are capable of proliferation to the level of normal spleen cell cultures in response to Fc fragments, but are incapable of making a polyclonal antibody response. The cell population that responds to the differentiation signal also responds to the proliferative signal. "Hot pulse" experiments demonstrated that proliferation precedes polyclonal activation.
Relationship between enhanced macrophage phagocytic activity and the induction of interferon by Newcastle disease virus in mice.
Authors: Hamburg S I , Cassell G H , Rabinovitch M
Published: December 2022

The relationship between phagocytic activity of peritoneal macrophages and serum interferon (IF) titers was evaluated in mice challenged with Newcastle disease virus (NDV). Time course studies indicated peak serum IF titers between 6 and 12 hr, whereas Fc receptor-mediated macrophage phagocytosis was maximal 18 hr after viral administration. Both responses decreased in parallel as the inoculated dose of the virus was reduced. Splenectomy, shown by others to decrease the NDV-induced serum IF titers, significantly decreased the stimulation of phagocytosis. The role of T cells in the response to the virus was studied with nude mice raised under germfree conditions. NDV-induced serum IF titers and macrophage phagocytosis were both diminished in BALB/c nudes compared with their heterozygous littermates. Both responses could be partially restored by transfer of thymocytes obtained from heterozygous mice. The results provide further evidence that in vivo macrophage stimulation by NDV is mediated by induced IF. The experiments with nude mice also indicate that the IF response to NDV is regulated by T lymphocytes.
Participation of lymphocyte activating factor (Interleukin 1) in the induction of cytotoxic T cell responses.
Authors: Farrar W L , Mizel S B , Farrar J J
Published: December 2022

The initiation of murine alloantigen-specific cytotoxic T cell responses is macrophage dependent. The requirement for macrophages can be replaced in macrophage-depleted cytotoxic T lymphocyte assay by a soluble factor released from phorbol myristic acetate-stimulated mouse peritoneal adherent cells or P388D1 macrophage tumor cells. On the basis of the cell of origin, m.w. (15,000), and elution profiles on DEAE cellulose and polyacrylamide gels, this macrophage-replacing factor for T cell-mediated cytotoxicity was identical to lymphocyte activating factor (LAF). The stimulatory effect of LAF was totally dependent on the presence of the priming alloantigen. The results presented in this report support the hypothesis that macrophage-mediated antigen-induced T cell activation is dependent on two signals, antigen and LAF.
The role in vivo of C3 and the C3b receptor in babesial infection in the rat.
Authors: Jack R M , Ward P A
Published: December 2022

The critical role of complement (C3) and the C3b receptor in facilitating the in vivo development of parasitemia with Babesia rodhaini in rats is documented. Depletion of serum C3 to less than 5% of normal levels by treatment of rats with the C3 inactivator isolated from cobra venom markedly delays the onset of parasitemia. Treatment of rats with trypan blue, an inhibitor of the C3b receptor, delays the development of parasitemia. Conversely, treatment of rats with suramin, a drug that blocks the C3b inactivator, markedly accelerates the progression of parasitemia and, correspondingly, the mortality rate. These observations suggest that the in vivo production of C3b and its interaction with C3b receptors on red cells and/or on parasites is a critical feature in babesial injection of rats. In support of the concept that B. rodhaini organisms contain C3b receptors, we have shown in vitro that parasites will activate the alternate complement pathway, resulting in uptake of radiolabeled C3, and that this uptake is blocked in the presence of trypan blue. Before and during the development of parasitemia, red cells become Coombs-positive for C3, but not for IgG. Taken together, the data support the vital role of C3 activation products (presumably C3b) and the C3b receptor in the facilitation of babesial infection in the rat.
Selective removal of T cell function from mouse lymphocyte suspensions by treatment with normal guinea pig serum.
Authors: Kierszenbaum F , Budzko D B , Miller H C
Published: December 2022

Treatment of murine spleen cells with normal guinea pig serum selectively abrogated responsiveness of these cells to the T cell mitogens PHA or Con A, but failed to affect responses to LPS, i.e., a B cell-specific mitogen. Although pretreatment with GPS inhibited the in vitro immune response of mouse splenocytes to SRBC, responses were normal after restoration with T cells only, indicating that B cells had been spared by GPS. Consistent with these results, incubation with GPS resulted in the loss of reactivity of mouse lymphoid cells in MLC as well as CML systems, both of which test for T cell activities. Furthermore, parental spleen cells treated with GPS were no longer capable of inducing a GVH reaction in F1 hybrids. When compared, the effects of GPS and anti-Thy-1.2 antibodies plus C were found to be comparable. These results indicate that GPS can selectively remove a number of T cell functions from heterogeneous murine lymphoid cell suspensions. Since spleen macrophages were insensitive to GPS cytotoxicity, lack of T cell function is not likely to be due to depletion of these accessory cells.
Resistance to fatal central nervous system disease by mouse hepatitis virus, strain JHM. II. Adherent cell-mediated protection.
Authors: Stohlman S A , Frelinger J A , Weiner L P
Published: December 2022

Resistance of SJL/J mice to intracranial inoculation with the JHM strain of mouse hepatitis, a coronavirus, is dependent upon the age of the animals at inoculation. Animals 12 weeks of age or older are resistant, whereas those 6 weeks or younger are uniformly susceptible to viral infection. Spleen cells or thioglycolate elicited peritoneal exudate cells can transfer resistance from 12-week-old to 6-week-old recipients. Removal of the adherent cells from either spleen or peritoneal cells ablated protection. Adherent cells from 12-week-old mice were protective even after depletion of Ia- and Thy-1-bearing cells. Antiviral antibody, thioglycolate injection into 6-week-old animals, and nylon wool-purified T cells were ineffective in mediating resistance. Adherent cells transferred 4 days before virus challenge, but not after challenge, were protective. Thus, there is an age-related change in SJL mice that protects from acute central nervous system disease, which may be due to maturation of a specialized adherent cell population.
In vivo responses to inhaled proteins. III. Inhibition of experimental immune complex pneumonitis after suppression of peripheral blood lymphocytes.
Authors: Shenker B J , Willoughby W F , Hollingdale M R , Mann T N
Published: December 2022

We have previously shown that inhaled Con A has a powerful enhancing effect on the formation of immune complexes between an inhaled antigen and circulating antibody. Immunohistochemical staining has demonstrated such complexes, together with host complement, in close association with foci of necrotizing destruction of the pulmonary parenchyma. We have postulated that Con A promotes immune complex formation indirectly through polyclonal activation of lymphocytes in the lung. In this paper we test this hypothesis in animals rendered unresponsive to Con A stimulation in vivo by i.v. administration of cholera toxin (CT). Such treatment raised the levels of cAMP in peripheral blood lymphocytes and inhibited their proliferative response to Con A in vitro. CT administration further blocked the local inflammatory response to intradermal injections of Con A, as well as the cell-mediated immune response to intradermal injections of BSA. Although CT failed to block the immune complex-mediated Arthus vasculitis in the skin, it did block production of immune complex pulmonary injury by antigen/mitogen aerosols, as did decomplementation with purified cobra venom factor. These findings support the hypothesis that polyclonal activation of pulmonary lymphocytes promotes immune complex-type alveolitis, possibly by facilitating interactions between humoral antibody and intra-alveolar antigen.
The syngeneic mixed leukocyte reaction: the genetic requirements for the recognition of self resemble the requirements for the recognition of antigen in association with self.
Authors: Yamashita U , Shevach E M
Published: December 2022

We have used cells from inbred strain 2 and strain 13 guinea pigs in order to define further the role of Ia antigens in the syngeneic mixed leukocyte reaction (MLR). The guinea pig syngeneic MLR resembled the autologous MLR in man in that it demonstrated both memory and specificity. The Ia antigens appeared to be the proliferative stimuli in that the primary stimulator cell was an Ia-positive adherent peritoneal exudate cell (PEC) and the reaction could be specifically inhibited by anti-Ia sera directed to the stimulator cell. We also demonstrated the existence of two (2 x 13)F1 T cell populations that were capable of reacting to one or the other parental PEC in the absence of any known exogenous antigen. These results suggest that the syngeneic MLR may represent T cell activation mediated through a receptor for self Ia.
Peanut agglutinin. V. Thymocyte subpopulations in the mouse studied with peanut agglutinin and Ly-6.2 antiserum.
Authors: London J , Horton M A
Published: December 2022

Thymocyte heterogeneity has been studied by the use of two cell surface markers--the Ly-6.2 alloantigen and peanut agglutinin (PNA) receptor. The previously described distribution of Ly-6 on corticoresistant and PNA binding to corticosensitive thymocytes has been confirmed. Double immunofluorescence labeling experiments in combination with techniques of physical enrichment for "mature" thymocytes have resulted in the identification of a novel subset of T cells carrying both the Ly-6 antigen and PNA receptors. Purification by fluorescence cell sorting of corticosteroid-treated thymocytes, labeled with monoclonal anti-Ly-2.2 antiserum, for phenotypically mature Ly-1+23-lymphocytes causes a concomitant enrichment in the proportion of Ly-6-positive cells, which lack the PNA receptor. The implications of these findings for the maturational pathways within the thymus are discussed.
The origins of alloreactivity: differentiation of prekiller cells to viral infection results in alloreactive cytolytic T lymphocytes.
Authors: Finberg R , Cantor H , Benacerraf B , Burakoff S
Published: December 2022

Mice maintained in our animal colony become primed to Sendai virus. This "environmental" priming is reflected in a shift in prekiller activity from the Ly 123 to Ly 23 T cell set and in increased virus-specific cytolytic activity. This transition is accompanied by the development of cytolytic activity against allogeneic targets (not expressing Sendai antigens). These findings are consistent with the view that continued stimulation of Ly 123 cells by autologous MHC antigens, associated with foreign antigens such as a virus, generate Ly 23 prekiller cells that respond to alloantigens as well as autologous cells infected with the relevant virus.
Functional effects of thymopoietin32-36 (TP5) on cytotoxic lymphocyte precursor units (CLP-U). I. Enhancement of splenic CLP-U in vitro and in vivo after suboptimal antigenic stimulation.
Authors: Lau C Y , Goldstein G
Published: December 2022

Cytotoxic lymphocyte precursor units (CLP-U) were enumerated in the spleens of C57BL/6 mice 3 days after i.p. injections of synthetic thymopoietin32-36 (TP5). One hundred to 1000 ng TP5/mouse potentiated splenic CLP-U, this effect being detectable only after suboptimal allogeneic sensitization (with 1.2 x 10(5) mitomycin-C treated DBA cells). This elevation of CLP-U persisted in the injected mice for at least 14 days. Control peptide did not affect CLP-U. In vitro incubation of 0.01 to 0.1 ng/ml of TP5 with normal C57BL/6 spleen cells also enhanced CLP-U after suboptimal allogeneic stimulation; high concentrations of TP5 caused suppression of CLP-U and this was detectable with optimal sensitization conditions. Thus TP5, in vitro and in vivo, appears to regulate immune responsiveness and this regulation varies with TP5 dosage and with the immune stimulus.
Preferential H-2 association in cytotoxic T cell responses to SV40 tumor-associated specific antigens.
Authors: Pfizenmaier K , Pan S H , Knowles B B
Published: December 2022

The primary cytotoxic T lymphocyte (CTL) response to the SV40 tumor-associated specific antigen (TASA) has been analyzed in H-2 recombinant mice of the H-2b,d,f,k,q,and s haplotypes, in F1 hybrid mice (of each combination of these six independent haplotypes), and in intra-H-2 recombinant mice. A gradation of responsiveness to SV40 TASA in association with the various H-2 K/D alleles is reported. A weak response is found in association with the H-2 Dd allele, which is strongly affected by the responder status in association with the other H-2 K/D region determinants of the immunized host. Analysis of CTL from F1 mice, after secondary in vitro restimulation with SV40-transformed cells from either parental strain, indicates that in vivo priming to SV40 TASA in association with each K/D associative allele does occur, although efficient CTL are found only in association with specific H-2 K/D determinants after primary immunization. Mechanisms to explain host control of the ability to generate effector T cells to the TASA of this oncogenic virus are discussed.
Antibody potential of human peripheral blood lymphocytes differentially expressing surface membrane IgM.
Authors: Thiele C J , Stevens R H
Published: December 2022

The appearance of circulating pokeweed mitogen-reactive B lymphocyte subpopulations responsible for the synthesis of IgM and IgG anti-tetanus toxoid antibody after in vivo booster immunization has been analyzed for differential expression of surface membrane IgM. B cells were rosetted with human mu-chain specific antiglobulin-coupled ox red blood cells and separated by density centrifugation into mu+ and mu- populations. After 8 days in vitro culture with irradiated T cells and pokeweed mitogen, antibody synthesis was assessed by quantitative radioimmunoassay. Mu+ cells synthesized both IgG and IgM anti-tetanus toxoid antibodies, whereas mu- cells predominantly synthesized IgG anti-tetanus toxoid antibodies. Limiting dilution analysis revealed a greater number of IgG anti-tetanus toxoid precursors in the mu+ population at all times after immunization compared with mu- cells. However, the activity, as measured by the amount of antibody produced per IgG anti-tetanus toxoid antibody precursor, was 2 to 4 times greater in the mu- population than that in the mu+ population. These results indicate that functionally distinct human circulating B lymphocytes can be identified by their differential expression of surface membrane IgM.
Distinction between C8-mediated and C8/C9-mediated hemolysis on the basis of independent 86Rb and hemoglobin release.
Authors: Gee A P , Boyle M D , Borsos T
Published: December 2022

The intermediate product EAC1-7 released hemoglobin when incubated with high concentrations of GPC8 in the absence of C9. The reaction failed to reach an end point within 8 hr at 37 degrees C, and analysis of the kinetics indicated that it did not conform to the one-hit theory of immune hemolysis, and was not, therefore, the result of C9 contamination of the C8 preparation. The release of 86Rb from labeled EAC1-7 incubated at 30 degrees C with limiting C8 and excess C9 was paralleled, within 5 to 10 min, by release of hemoglobin. In the absence of C9 and with higher concentrations of C8, 86Rb was released rapidly, but hemoglobin release was delayed for several hours. Addition of excess C9 to concentrations of C8, which did not alone cause 86Rb release, resulted in substantial release of the isotope. These observations indicate that C9 acts by producing a distinct lesion in the cell membrane rather than by accelerating the release of hemoglobin from the C8-initiated 86Rb-releasing lesions. It is concluded that 86Rb release cannot be used as a reliable indicator of cell lysis and that C8- and C8/C9-mediated hemolysis are the result of mechanistically different processes.
Identification of Ia on a subpopulation of human T lymphocytes that stimulate in a mixed lymphocyte reaction.
Authors: Schuurman R K , Gelfand E W , Matheson D , Zimmerman B , Dosch H M
Published: December 2022

The delineation of discrete subpopulations of human T lymphocytes has permitted preliminary analyses of the complex cellular network regulating the immune response in man. We previously showed that a subset of T lymphocytes, designated as theophylline-sensitive because of their inability to bind sheep red blood cells in the presence of the drug, are responsible for antigen-specific suppression or regulation in an in vitro plaque-forming cell assay. We now show that 25 to 45% of these theophylline-sensitive T cells were Ia-positive by immunofluorescence with a rabbit antiserum raised against purified B lymphoblast surface antigenic material. These data suggested that 4 to 7% of peripheral blood T cells carry Ia determinants. The presence of Ia determinants on this T cell subset was confirmed by gel analysis of radioiodinated surface material. Furthermore, in mixed lymphocyte culture, the theophylline-sensitive cells demonstrated HLA-D determinants and were 10-fold more potent stimulators than equal numbers of B lymphocytes. The presence of Ia determinants on these T cells indicates the expression of major histocompatibility complex-related regulatory gene products on a specific human T lymphocyte subpopulation.
Biochemical characterization of lymphocyte regulatory molecules. II. Purification of a class of rat and human lymphokines.
Authors: Gillis S , Smith K A , Watson J
Published: December 2022

Rat spleen cells activated in vitro by concanavalin A produce lymphokine molecules that possess biologic activity in a number of murine lymphocyte response assays. A single class of lymphokine most adequately described as T cell growth factor (TCGF, Interleukin-2) with a m.w. of 15,000 as estimated from gel filtration studies and with an isoelectric range of 5.4 to 5.6 stimulates i) the growth of established T cell lines in culture, ii) the proliferation of thymocytes in the presence of Con A under culture conditions where Con A alone is non-mitogenic, iii) the induction of antibody responses to heterologous erythrocyte antigens in athymic (nude) mouse spleen cell cultures, and iv) the generation of cytotoxic T lymphocytes (CTL) in thymocyte cultures and in nude mouse spleen cell cultures. We suggest that in each of the assay systems tested, this class of rat lymphokine acts directly on activated T cells. Nonactivated T cells must be stimulated by either mitogen or antigen before becoming responsive to lymphokine, but do not require antigen or mitogen for continued lymphokine-dependent proliferation. Similarly, human peripheral blood mononuclear cells activated by phytohemagglutinin (PHA) produce a class of lymphokines of identical size with an isoelectric point of 6.0 to 6.5 that possess the same biologic properties as measured in murine lymphocyte response systems.
Idiotype-specific tolerance: preferential alteration of idiotype expression after neonatal exposure to tolerogen.
Authors: McKearn J P , Quintáns J
Published: December 2022

The development of HOPC-8 idiotype-positive and HOPC-8 idiotype-negative B cell subpopulations involved in the immune response to a single PC antigen, has been monitored during normal differentiation and in situations where neonatal tolerance had been induced. It was found that H8 id+ and H8 id- anti-PC antibody-secreting cells appeared at approximately the same time in ontogeny and these late maturing subsets constituted equal fractions of the immune response in CBA/CaJ X BALB/c F1 (JBF1) mice. However, when JBF1 mice were injected at birth with graded doses of PC-FGG, responses obtained in 4-week-old mice were predominantly of the H8 id. This PC-specific, idiotype-restricted, unresponsive state was stable upon adoptive transfer. Specific depletion of Thy-1.2-positive cells and in vitro "mixing" experiments involving combined ratios of tolerant and nontolerant spleen cells suggest that the unresponsive state measured 4 weeks after tolerogen administration does not involve suppressor cells. It would appear that intrinsic differences between these idiotypically defined B cell subsets account for the observed differential susceptibility to tolerance induction among PC-responsive B cells.
BCG-induced enhancement of endotoxin sensitivity in C3H/HeJ mice. I. In vivo studies.
Authors: Vogel S N , Moore R N , Sipe J D , Rosenstreich D L
Published: December 2022

C3H/HeJ mice exhibit a marked insensitivity to bacterial lipopolysaccharide (LPS) in vivo. Pretreatment of these mice with viable BCG organisms 11 days before LPS administration renders them sensitive to the lethal effects of a highly purified, phenol-extracted LPS. Other in vivo responses to LPS are increased in BCG-infected C3H/HeJ mice in parallel with enhanced lethality. These include 1) the elevation of serum interferon, 2) the production of the acute phase reactant, serum amyloid A (SAA), and 3) hypoglycemia. However, BCG infection has only a minimal effect on anti-LPS antibody production. BCG-infected C3H/HeJ mice approach the LPS sensitivity of normal C3H/HeN mice, but the enhanced LPS sensitivity is transient and decreases over a 2-month period. The ability of BCG to induce LPS sensitivity in C3H/HeJ mice demonstrates that LPS unresponsiveness is not due to an absolute defect in this strain, but rather, a partially reversible state of hyporesponsiveness. In addition, these findings, in conjunction with other observations, suggest that the enhancement of LPS sensitivity induced by BCG infection is mediated primarily through an effect on T cells and/or macrophages rather than B lymphocytes.
The fundamental T cell proliferative repertoire in a nonresponder strain and its qualitative alteration by suppression.
Authors: Yowell R L , Araneo B A , Sercarz E E
Published: December 2022

B10 mice, although genetically nonresponsive to hen egg-white lysozyme (HEL) after i.p. immunization due to suppressor T cells, make a vigorous helper and proliferative T cell response in the draining popliteal lymph nodes (P-LN) soon after footpad immunization with HEL. The fundamental specificity repertoire in B10 P-LN analyzed with cross-reactive lysozymes, was then compared with that found after the delayed appearance of suppression, in the PETLES. In contrast with B10.A mice, whose T cell specificity pattern was unchanged with time, or anatomical site, the onset of HEL-induced suppression in B10 mice led to a marked heteroreactive shift in specificity pattern. This shift did not occur after immunization with REL (ring-necked pheasant lysozyme), which fails to induce suppression.
Immunomodulation by Corynebacterium parvum in normal humans.
Authors: Hokland P , Ellegaard J , Heron I
Published: December 2022

Four normal human donors were immunized with 2 mg of heat-killed Corynebacterium parvum by subcutaneous and intracutaneous injections, and lymphocyte surface markers, antibody-dependent (ADCC), and spontaneous cell-mediated (SCMC) cytotoxicities followed for a 28-day period. Although no changes were observed in the relative proportions of B, T, and Fc receptor-carrying lymphocytes, two T cell subpopulations, namely, the autologous rosette-forming cells and active rosette-forming cells, both exhibited significant increases. Significant increases were also demonstrated in the proportion of monocytes carrying Fc receptors and in the proportion of monocytes phagocytizing Latex beads. Although no consistent changes could be found in ADCC against the P 815 mastocytoma cell line, the SCMC against both the myeloid leukaemia line K 562 and the lymphoma line RAJI was found to be elevated as early as 6 hr post-vaccination. The possibility that the enhanced SCMC activity was induced in vivo by interferon was supported thus: 1) Enhancement of SCMC in vitro by interferon was abrogated by the vaccination. 2) Serum interferon determinations showed significant increases in parallel with the lack of in vitro SCMC enhancement.
Endogenous pyrogens made by rabbit peritoneal exudate cells are identical with lymphocyte-activating factors made by rabbit alveolar macrophages.
Authors: Murphy P A , Simon P L , Willoughby W F
Published: December 2022

Purified endogenous pyrogen (EP), isolated in one laboratory from stimulated rabbit peritoneal exudate cells (PEC), was compared with purified lymphocyte activating factor (LAF), isolated in another laboratory from stimulated rabbit alveolar macrophages (AM). Both EP and LAF occurred in two forms, one with an isoelectric point (pI) of 7.3 to 7.4, the other with a pI of 4.6 to 4.7. Both forms of EP and LAF had m.w. of 13,000 to 16,000 daltons as judged by gel filtration. Both forms of EP had LAF activity, and both forms of LAF were pyrogenic. The pI 7.3 EP, which is known to have an -SH group essential for its biologic activity, bound to Thiol Sepharose columns and could be eluted with mercaptoethanol. The pI 7.3 LAF behaved in exactly the same way. Furthermore, antisera from three different goats were available that completely blocked the pyrogenicity of pI 7.3 EP in vivo; these sera also blocked the pI 7.3 LAF activity in vitro. The pI 4.6 EP and LAF did not bind to Thiol Sepharose columns, nor were they inhibited by any of the antisera that blocked the pI 7.3 EP and LAF. Moreover, isoelectric focusing of pI 4.6 EP in very shallow gradients revealed microheterogeneity with sharp peaks of EP activity observed at pH 4.6 and 4.7. Analysis for LAF activity showed an identical microheterogeneity. These results are consistent with the idea that EP and LAF are identical.
Lack of gene complementation prevents expression of I-Ek in recombinant A.TFR5.
Authors: Lafuse W P , McCormick J F , David C S
Published: December 2022

The I-E molecule is produced by complementation of genes in I-A (Ae) and I-E (E alpha). Ia specificities 22 and 23 are generated by the hybrid molecule, whereas Ia.7 is an allotypic determinant presumably on the alpha-chain of the I-E molecule. Recombinant A.TFR5 (AfEk) lacks detectable I-E molecule since Af and Ek cannot complement. In a cross between A.TFR5 and B10.A(4R) (AkEb), Aek and E alpha k can successfully complement to express the I-Ek molecule on the cell surface of the heterozygote. Haplotypes H-2b and H-2s can also provide the permissive Abe and Ase molecules for complementation with Ek alpha of A.TFR5.
Fine specificity and idiotypes of early antibodies against (4-hydroxy-3-nitrophenyl)acetyl (NP).
Authors: Karjalainen K , Bång B , Mäkelä O
Published: December 2022

Earlier studies have demonstrated that antibodies of the primary response (days 14 to 30) to (4-hydroxy-3-nitrophenyl)acetyl (NP) of C57BL, LP, and 101 mice share idiotype NPb and are heteroclitic (the affinity for certain chemical analogues of NP is higher than the affinity for NP), whereas BALB/c antibodies share idiotype NPa and are homoclitic. Both idiotypes are inherited as allotype-linked traits and have the lambda-chain as the predominant light chain. This study was extended to earlier anti-NP antibodies (7 days) of eight mouse strains (42 individuals) and to anti-NP hybridoma proteins originating from day 6 spleen cells. Only one of the early 42 antisera was found to be homoclitic, and no genetic polymorphism was detectable in fine specificity. In contrast, idiotypes NPa and NPb still followed the genetic rules that had been established earlier. lambda-Chain-bearing BALB/c hybridoma proteins from day 6 of the primary response were more heteroclitic than kappa-chain bearing ones (Krel greater than 20), but two out of three kappa proteins were also heteroclitic (Krel approximately 2). Our results caution against the use of the heteroclitic fine specificity as a typing method. In contrast, they reinforce the value of anti-idiotypic antibodies for this purpose.
Antigen-antibody complexes generate Lyt 1 inducers of suppressor cells.
Authors: Rao V S , Bennett J A , Shen F W , Gershon R K , Mitchell M S
Published: December 2022

Pretreatment of H-2b mice with KCl-extracts of an H-2d tumor (L1210) together with L1210 antibody rendered the mice incapable of mounting an effective immune response to viable L1210 tumor cells. This specific immunosuppression was associated with inhibition of macrophage functions, which could be used to quantitate the level of suppression. Lyt 1 cells (but not Lyt 2 cells) from either the spleen or thymus of mice pretreated with antigen-antibody complexes could adoptively transfer the suppressed state to normal mice. The Lyt 1 cells that transferred the suppression were resistant to low (20 mg/kg) doses of cyclophosphamide (Cy) but required a Cy-sensitive precursor and/or amplifier cell to be activated. Once activated, they required a Cy-sensitive Lyt 1 2 3 acceptor cell in the normal recipient to effectively suppress the adoptive host's macrophages. Our results indicative that immune complexes in concert with a Cy-sensitive T cell generate Cy-resistant Lyt 1 inducers of suppression. These in turn activate normal thymic or peripheral Lyt 1 2 3 acceptor cells, resulting in the generation of effector suppressor T cells. These suppressor cells are most likely the proximate cause of the inhibition of macrophages we have observed in vivo.
Partial N-terminal amino acid sequences of guinea pig classic histocompatibility antigens.
Authors: Schwartz B D , McMillan M , Shevach E , Hahn Y , Rose S M , Hood L
Published: December 2022

Partial N-terminal amino acid sequences were determined by microsequencing for three of the guinea pig GPLA-B classic histocompatibility antigens, which are presumably allelic products. The sequences of GPLA-B.1 derived from the noncongenic inbred strain 2 and strain 13 animals showed no differences a their N-termini, suggesting that these molecules are chemically as well as serologically identical. Two residues, isoleucine and leucine, were found at position 5 of the sequence of GPLA-B.1, suggesting that GPLA-S, the product of the second classic histocompatibility locus, was being cosequenced. GPLA-B.2 and GPLA-B.3 antigens showed distinct sequence differences from GPLA-B.1 and from each other. The sequences of GPLA-B.3 derived from a random-bred guinea pig and from the inbred DHCBA strain showed no differences and showed a possible species specific residue. All sequences showed significant homology with histocompatibility antigens of other species, suggesting a common evolutionary origin.
Identification of the immunosuppressive components of canine pulmonary surface active material.
Authors: Ansfield M J , Benson B J
Published: December 2022

Pulmonary surface active material (SAM), purified from canine lung lavage fluids, is a phospholipid-rich lipoprotein with potent immunosuppressive activity. Experiments were performed to identify those components of SAM that were responsible for this immunosuppressive effect. Results indicated that the lipid, and not the protein, fraction of SAM was immunosuppressive. Two phospholipids, phosphatidylglycerol and phosphatidylcholine, were identified as the predominant immunosuppressive components of the SAM-lipid fraction. lymphocyte proliferation in response to mitogenic or allogeneic stimulation was suppressed by intact SAM, SAM-lipid, phosphatidylglycerol, and phosphatidylcholine. Each of these preparations inhibited RNA, protein and DNA synthesis by mitogen-stimulated lymphocytes. Antioxidants consistently failed to diminish the immunosuppressive properties of SAM or its lipid components. The mechanism of this immunosuppressive action of SAM and its phospholipid components remains undefined. Our data indicate, however, that it is unlikely to be due either to cytotoxicity or to an artifact of lipid oxidation in vitro.
Basilea rabbit immunoglobulins: detection and characterization by specific alloantiserum.
Authors: Good P W , Notenboom R , Dubiski S , Cinader B
Published: December 2022

Evidence is provided for the existence of the Fbbas (Basilea) gene product (allotype). Specific antisera were raised by immunization of rabbits that did not possess the Basilea genes. With the help of these antisera, the Basilea allotype was detected in sera from rabbits, homozygous and heterozygous with respect to Basilea gene. The Basilea gene is expressed on a very low proportion of immunoglobulin molecules. The isoelectric point of the Basilea light chains is distinct from that of the lambda-light chains (peaks at pH 4.7 and 5.5, respectively). Sera from a large proportion of Ab9-positive rabbits of the Basel Institute for Immunology that were heterozygous at the Ab locus reacted with the anti-Basilea serum, even though they could no possess the Basilea gene at the Ab locus. Sera from Ab9-positive rabbits from Toronto were Basilea-negative. It was suggested that Ab9 and Basilea allotypes are controlled at closely linked loci. Ab9 haplotype prevalent in the Basel animal colony, possesses both Ab9 and Basilea genes, whereas the corresponding Toronto haplotype has only the Ab9, but not Basilea gene. The formation of the Basilea genotype was attributed to a crossing over, during which the Ab9 and Basilea genes separated.
Host defenses in experimental scrub typhus: mapping the gene that controls natural resistance in mice.
Authors: Groves M G , Rosenstreich D L , Taylor B A , Osterman J V
Published: December 2022

Natural resistance of mice to lethal ifections of Rickettsia tsutsugamushi, strain Gilliam, is controlled by a single, autosomal, dominant gene, which we have designated Ric, with r and s representing the resistant nd susceptible alleles, respectively. Using three sets of recombinant inbred mouse strains (BXD, BXH, and BXJ), the Ric locus was mapped to Chromosome 5 closely linked to the retinal degeneration (rd) locus. This linkage was confirmed by a backcross analysis. Based on the RI strains and the C57BL/6Ty-le congenic strain (the only proven Ric-rd cross-over), we estimate the recombination frequency between Ric and rd to be 0.015. Three presumptive Ric-rd recombinants detected among 93 backcross mice may represent caes of incomplete penetrance of the resistance allele rather than recombination. Analyis of th C57BL/6JTy-le congenic strain indicates that Ric is proximal to rd on Chromosome 5. If so, the correct gene order is Pgm-1-W-Ric-rd-Gus.
A monoclonal antiidiotypic antibody to MOPC 315 IgA inhibits the growth of MOPC 315 myeloma cells in vitro.
Authors: Mahony J , Bose A , Cowdrey D , Nusair T , Lei M , Harris J , Marks A , Baumal R
Published: December 2022

Spleen cells from BALB/c mice immunized with MOPC 315 IgA were fused with P3X63/Ag8 myeloma cells. Hybrid clones were screened for antibody production by a plate-binding radioimmunoassay in which MOPC 315 IgA was reacted with culture supernatants and 125I-protein A. One antibody-producing hybridoma clone (D10) was selected and injected i.p. into BALB/c mice. Ascitic fluid of tum or-bearing animals reacted specifically with MOPC 315 IgA and the reaction was inhibited by DNP- aminocaproic acid, indicating that the monoclonal antibody was directed against the hapten-binding site of MOPC 315 IgA. The monoclonal antiidiotypic antibody was of the complement (C)-binding IgG2a subclass and inhibited IgA production and growth of MOPC 315 cells in vitro in the presence of guinea pig C, as assessed by inhibition of formation of plaques and colonies by MOPC 315 cells in agar.
Use of monoclonal antibody to immunochemically characterize variant-specific surface coat glycoprotein from Trypanosoma rhodesiense.
Authors: Lyon J A , Pratt J M , Travis R W , Doctor B P , Olenick J G
Published: December 2022

Monoclonal antibodies were employed to study the molecular basis for charge heterogeneity in variant-specific surface coat glycoprotein prepared from clone CP3B4 of the Wellcome strain of Trypanosoma rhodesiense. Thirteen hybridomas secreting monoclonal antibodies specific for CP3B4 were obtained by fusing murine plasmacytoma cells to spleen cells from mice immunized with purified surface coat glycoprotein. The clone population of CP3B4 trypanosomes was shown to be homogeneous by means of immunofluorescent assays using culture supernatants from each of the 13 hybridomas. No cross-reactivity was found with other variant antigenic types of the same serodeme. Ascitic fluids were generated from 4 of the hybridomas and th molecular and epitopic specificities of the fluids or their IgG fractions were determined isoelectrofocusing of immunoprecipitates of radioiodinated glycoprotein antigen followed by autoradiography revealed that all 3 major components of the charge heterogeneous CP3B4 surface-coat glycoprotein were immunoprecipitated by each of the 4 monoclonal IgG fractions. Immunofluorescent staining of live trypanosomes was obtained with only one of the 4 ascitic fluids. The results show that charge heterogeneity does not derive from a heterogeneous population of parasites. Furthermore, the data indicate that there are at least 2 different epitopic specificities exhibited by the monoclonal antibodies tested and that each of the 3 charge heterogeneous components of the surface coat glycoprotein contains these epitopes. Charge heterogeneity of CP3B4 surface coat glycoprotein may be attributed to post-translational modification or to limited proteolysis.
Regulation of clones responding to dextran B1355S. II. Response of T-dependent and T-independent precursors.
Authors: Ward R , Kohler H
Published: December 2022

The existence of precursors for TI and TD alpha 1 leads to 3 dextran antigens in BALB/c mice was demonstrated. A T-dependent dextran antigen was prepared by coupling dextran B1355S to hemocyanin and subsequent digestion with dextranase. The PFC response of BALB/c mice primed with hemocyanin to dextran-hemocyanin was found to be 8 times higher than in unprimed animals. The splenic focus assay was adapted for the analysis of precursors responding to T-dependent and T-independent dextran antigens. Pretreatment of recipients with anti-thymocyte serum abolished the response in fragment cultures to dextran-hemocyanin but did not affect the response to dextran B1355S. The frequencies of precursors in the adult BALB/c mouse responding to dextran and dextran-hemocyanin were determined by limiting dilution analysis. The frequency of T-dependent precursors was found to be almost 3 times greater than the frequency of T-independent precursors.
Biosynthesis and cell surface localization of nonglycosylated human histocompatibility antigens.
Authors: Ploegh H L , Orr H T , Stominger J L
Published: December 2022

The effects of the inhibitor of N-linked glycosylation, tunicamycin, on the synthesis of HLA-A and -B antigens in the human lymphoblastoid cell line JY are described. HLA-A and -B antigens are membrane glycoproteins that consist of a two chain complex, the heavy chain being glycosylated at Asn 86, whereas the light chain, identical to beta 2-microglobulin, is not glycosylated. HLA-A and -B antigens synthesized in the presence of the antibiotic are devoid of carbohydrate. This lack of carbohydrate does not affect the association of the heavy and light chains, nor does it affect the reactivity with human alloantisera, or a mouse monoclonal antibody W6/32, that reacts with all HLA-A and -B specificities examined so far. Nonglycosylated HLA-A and -B antigens are no more susceptible to proteolysis with trypsin, chymotrypsin, or papain than their fully glycosylated counterparts. Thus it may be concluded that the carbohydrate side chains of HLA-A and -B antigens do not contribute significantly to the conformation of HLA-A and -B antigens, at least as measured by these procedures. Pulse-chase experiments, in conjunction with the isolation of cell-surface HLA-A and -B antigens by adsorbing the monoclonal antibody W6/32 to intact cells, indicate that nonglycosylated molecules reach the cell surface at a rate indistinguishable from that of fully glycosylated molecules (although the absolute amount synthesized in the presence of tunicamycin was decreased). Thus glycosylation is also not required for membrane insertion of HLA antigens, nor for their subsequent transport to the cell surface.