bluuebunny/crossref_metadata_2025 huggingface dataset:
Thymus-Derived Lymphocyte-Dependent Rejection of Syngeneic Papovavirus (SV40) and Methylcholanthrene Tumors in Inbred Hamsters
Authors: Blasecki John W.
Published: December 2022

Treatment of specifically sensitized MHA hamster lymphoid cells with rabbit antisera specific for hamster thymusderived lymphocytes, in the presence of C, eliminated those cells capable of inhibiting the growth of syngeneic SV40 and methylcholanthrene tumors in vivo. Thymectomized, lethally-irradiated, bone marrow-reconstituted hamsters, shown to be devoid to T cell function, were, after attempted specific sensitization to the two syngeneic tumor cell lines, unable to reject either tumor by direct challenge in vivo. In addition, lymphocytes from such animals were incapable of inhibiting the growth of either tumor cell line in normal syngeneic recipients in the tumor cell neutralization assay. These data strongly support the conclusion that specifically sensitized thymus-derived lymphocytes are required for the rejection of syngeneic SV40 and methylcholanthrene tumors in inbred hamsters.
Spontaneous Cytotoxicity of Human Peripheral Mononuclear Cells Toward Red Blood Cell Targets in Vitro
Authors: Muchmore Andrew V. , Decker Jean M. , Blaese R. Michael
Published: December 2022

Human peripheral blood mononuclear cells become spontaneously cytotoxic toward a broad range of erythrocyte targets after 6 to 7 days in culture. The presence of high concentrations of fetal calf serum (20%) inhibits the development of spontaneous cytotoxicity, whereas low concentrations (1 to 2%) markedly enhance cytotoxicity. Allogeneic, xenogeneic, and even syngeneic RBC are suitable targets, suggesting little, if any, target cell specificity. The addition of excess unlabeled RBC inhibits 51Cr release from both identical and totally unrelated RBC targets; further arguing that the cytotoxic effector cell is not directed toward one and only one antigenic specificity on the target. Cell separation techniques employed at the beginning of culture demonstrate that cytotoxicity is markedly enhanced by T cell depletion by using a SRBC rosetting technique. Removal of phagocytic cells by incubation with iron particles and a magnet substantially depletes subsequent cytotoxic potential. EA rosette depletion of cells also markedly reduces subsequent cytotoxic potential. Interestingly, EA rosette depletion at the end of 7 days in culture has almost no effect on cytotoxicity, whereas E rosette depletion after 7 days continues to enhance cytotoxicity. Depletion of the cultured effector cell populations over a nylon wool column or with iron and a magnet abolished cytotoxicity. These results suggest that the cell responsible for spontaneous RBC cytotoxicity is a non-T cell which initially expresses an easily detectable Fc receptor and exhibits surface adherence properties. However, after 7 days in culture the cytotoxic cell either no longer expresses an Fc receptor, or its affinity, density, or availability are somehow altered in vitro.
Venom of the Ant Pseudomyrmex Sp.: Further Characterization of Two Factors That Affect Human Complement Proteins
Authors: Schultz Duane R. , Arnold Patricia I.
Published: December 2022

Two factors in the venom of the tropical ant Pseudomyrmex sp. had potent anti-complementary activity. The first (F1) was resistant to boiling and had the properties of a polysaccharide or glycoprotein. It had no effect on purified C4 and C2, but caused activation of C1, resulting in the consumption of C4 and C2 in normal human serum. F1 appeared to activate C1 by forming a complex with a nonimmunoglobulin factor in normal human serum. The serum factor was not C1q. The second venom factor (F2) was heatlabile (56°C, 30 min), and was identified as a tryspin-like enzyme. It hydrolyzed α-N-benzoyl-dl-arginine p-nitroanilide HCl and was inhibited by soybean trypsin inhibitor, but not by EDTA. It caused inactivation of purified complement components, but not components in serum, presumably because of natural serum inhibitors. F1 and F2 were closely associated in native ant venom. After gel filtration of the venom, two complement inactivators were eluted. They had m.w. of 175,000 and 32,500 daltons, but F1 and F2 were associated with both m.w. species. F1 and F2 migrated together after electrophoresis on polyacrylamide gels, and both were identified in the ultrafiltrate of ultrafiltration membranes having an m.w. cut-off of 10,000 daltons.

The results of this report and our previous studies (see Reference 11) show that ant venom is a potent activator/inactivator of components in both the classical and alternative complement pathways.
Synthesis and Release of Thymidine by Macrophages
Authors: Stadecker Miguel J. , Calderon Jesus , Karnovsky Manfred L. , Unanue Emil R.
Published: December 2022

An inhibitor of DNA synthesis and cell proliferation found in macrophage supernatants was subjected to further analysis. The following conclusions were drawn: a. Biochemically, the inhibitor appeared to be thymidine, judging from the migration in three different thin-layer systems and on gel filtration. b. The inhibitor was shown to be synthesized de novo by macrophage monolayers pulsed with a radiolabeled precursor of thymidine such as 14C-formate. c. The amount of inhibitor present in tissue culture fluids proved to be sufficient to block the growth of the EL-4 leukemia cell line in a manner that could be prevented with the addition of 2′-deoxycytidine. The EL-4 line was considerably more sensitive to thymidine blockade than a number of different cells tested.
Soluble Factors in Tolerance and Contact Sensitivity to Dnfb in Mice
Authors: Moorhead John W.
Published: December 2022

Active suppression of contact sensitivity to DNFB in mice is mediated by a·soluble suppressor factor (SSF) which is released in vitro by cultures of LN cells that contain antigen-specific suppressor T cells. For SSF-mediated suppression to occur, identity is required among genes in the H-2 complex between the donor of SSF and the donor of DNFB-immune LN cells. Identity in either the left half or right half of the H-2 complex was found to be both sufficient and required. Additional experiments using congeneic strains with intra-H-2 recombinants showed that the genetic homology which was required mapped to genes contained in the H-2K and/or H-2D regions of the H-2 complex.
Chemical and Biological Properties of a Protein-Rich Fraction of Bacterial Lipopolysaccharides
Authors: Morrison David C. , Lindsay Leroy , Betz Sally J.
Published: December 2022

Lipid A-associated protein (LAP) isolated from preparations of bacterial lipopolysaccharides (LPS, endotoxins) has been demonstrated to initiate the release of amines from rat peritoneal mast cells. The release at low concentrations of LAP requires both cellular energy and calcium, and thus appears to be a true secretory response. At higher concentrations the release is independent of these variables. The time required for maximal response is approximately 10 to 15 min at 37°C. The response appears to be a general property of Escherichia coli LAP preparations since LAP isolated from three serotypes of these organisms all have similar activity. On the basis of heat lability at 100°C, the ability of LAP to initiate mast cell secretion appears to be independent of its ability mitogenically to stimulate murine B lymphocytes.
Complementation Between Genetic Variants Affecting the Response of Chicken Leukocytes to Concanavalin A
Authors: Pink J. Richard , Miggiano Vincenzo C.
Published: December 2022

Birds of the partially inbred G-B1 chicken line can be classified as either high or low responders to Con A, on the basis of the amount of 3H-thymidine incorporated by Con A-containing cultures of their peripheral blood leukocytes. The pattern of inheritance of the high and low responder traits suggests that the variation in response is due to genetic polymorphism at a single autosomal locus. However, the allele responsible for the low responder trait of the G-B1 line is not identical to the allele of the previously described Mr1 locus carried by the inbred low responder CC line, since (CC × G-B1 low responder)F1 birds are uniformly high responders to Con A.

The responses to Con A of mixtures of CC and G-B1 low responder cells are not significantly higher than the responses of either component of the mixture alone. Thus, the gene products responsible for the complementation observed in F1 hybrids cannot complement extracellularly, and are not readily transferable from one cell to another.
Late Acting T Cell Depression of High Avidity IgG Antibody Secretion in the Secondary Response
Authors: Warren Robert W. , Davie Joseph M.
Published: December 2022

Activated T lymphocytes (ATC) suppressed the expression of high avidity plaque-forming cells (PFC) in the secondary immune response when given in vivo 1 day before assay or when mixed in vitro with hyperimmune cells for 90 min before assay. This late acting suppression is a cell dose-dependent, carrier-specific, T cell-mediated phenomenon. The target of this activity is probably the antibody-secreting cell.
Studies on the Cytolytic Activity of Human Lymphocytes
Authors: Ziegler H. Kirk , Geyer Carl , Henney Christopher S.
Published: December 2022

The binding of human K cells to antibody-coated cell monolayers and to immobilized immune complexes was studied under a variety of experimental conditions. Binding could be demonstrated by the depletion of K cell activity in the nonadherent cells as well as the augmentation of lytic activity in the adherent cell fraction. A selective binding of K cells was shown by experiments in which τ90% of K cell-mediated lytic activity was depleted while only 10% of the total lymphocytes were bound.

K cell binding was inhibited by staphylococcal protein A (SPA) indicating a a dependence on interactions between the Fc portion of IgG and homologous Fc receptors. K cell binding was partially inhibited by cytochalasin B and by low temperature (0°C) but was unaffected by the absence of divalent cations or by the presence of cAMP-“active” drugs.

Both SPA and cytochalasin B inhibited the K cell-mediated lysis of target cells coated with low amounts of antibody. This inhibition was reversed, however, by increasing the antibody “coat”. In contrast, inhibition of cytolysis by EDTA and by drugs that raised cAMP levels in human lymphocytes could not be reversed by increasing the amount of target cell-associated antibody.

These findings allow a clear dissection of K cell-mediated cytolysis into two independent events, with distinctive requirements: a binding phase involving K cell-target cell interaction and a lytic phase which follows such accomodation.
The Ontogeny of Thymic Independent Antibody Responses in Vitro in Normal Mice and Mice with an X-Linked B Cell Defect
Authors: Mosier D. E. , Mond J. J. , Goldings E. A.
Published: December 2022

The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other.
Effect of Lipopolysaccharide on Immunogenicity and Tolerogenicity of HGG in C57BL/6J Nude Mice: Evidence for a Possible B Cell Deficiency
Authors: Parks D. Elliot , Doyle Michael V. , Weigle William O.
Published: December 2022

Studies were performed to define the in vivo and in vitro responsiveness of nude mice to bacterial lipopolysaccharide (LPS). The in vitro responsiveness to LPS of spleen cells from congenitally athymic nude C57BL/6J mice was equivalent to littermate cells when monitored by stimulation of mitogenesis or polyclonal activation. Additionally, although nude spleen cells were incapable of responding to in vitro challenge with the T-dependent antigen, sheep red blood cells (SRBC), the addition of LPS to these cultures promoted specific antibody synthesis indicating classical responsiveness of nude B cells to LPS in vitro. The effects of LPS upon responsiveness to human γ-globulin (HGG) in vivo were also investigated. The injection of deaggregated HGG (tolerogen) into nude mice was demonstrated to induce immune tolerance in the splenic B cells of these mice. This unresponsive state was stable upon transfer into primed, irradiated recipients and persisted in the nude mice for up to 4 months. The induction of this tolerant state established in the absence of detectable T cell activity could be inhibited by the injection of LPS 3 hr after the tolerogen. Although LPS was capable of inhibiting the induction of tolerance in nude mice in vivo, it was incapable of promoting the generation of specific antibody-secreting, plaque-forming cells (PFC) to either HGG or SRBC when injected with these T-dependent antigens. This failure of LPS to replace the requirement for T cells in the production of the PFC response to these antigens did not extend to AT × BM littermate mice. Additionally, LPS itself was recognized as a T-independent antigen by these nude mice. Although the induction of tolerance in the B cells of nude mice demonstrated that T cells are not required for the induction or maintenance of B cell tolerance, the inability of nude B lymphocytes given LPS to respond to T-dependent antigens indicated that the signal received by B cells from the LPS molecule which replaces the requirement for helper T cells may be distinct from other LPS signals. Furthermore, the data from several experimental approaches suggested that nude mice may be deficient in a subpopulation of B cells which is responsive to both antigen and nonspecific B cell activators in normal mice.
Generation of T Helper Cells in Vitro
Authors: McDougal J. Steven , Cort Sheila P. , Gordon David S.
Published: December 2022

Thymocyte-macrophage cultures primed with carrier protein release an alloantigen-related factor that enhances the anti-hapten plaque-forming cell response of hapten-primed spleen cells in vitro. Use of immunoadsorbant columns made with a variety of alloantisera indicates that the relevant antigens in this system are coded for by the H-2 major histocompatibility locus in mice. The data indicate that in H-2d and H-2k strains the important genetic regions are in the I region between the K region and the I-C subregion and suggest, based on current understanding of Ia specificities, that the I-A subregion codes for these antigens.
Experimental Allergic Uveitis. Isolation, Characterization, and Localization of a Soluble Uveitopathogenic Antigen from Bovine Retina
Authors: Wacker Waldon B. , Donoso Larry A. , Kalsow Carolyn M. , Yankeelov John A. , Organisciak Daniel T.
Published: December 2022

The soluble antigen involved in the pathogenesis of EAU was isolated from bovine retinal extract by precipitation with ammonium sulfate followed by molecular sieve and ion exchange chromatography. The purified fraction formed a double precipitin band by immunodiffusion and immunoelectrophoresis, and a doublet by analytical disc electrophoresis. By immunodiffusion one of these components formed a reaction of identity with guinea pig S antigen and the other a reaction of partial identity. Because the two components had the same m.w. and similar electric mobility, they are presumed to be minor structural variants of the same molecule.

The purified antigen had a m.w. of approximately 102,000 by analytical ultracentrifugation, 50,500 by SDS electrophoresis, and 56,000 by gel filtration chromatography. Sedimentation velocity studies with increasing concentrations of antigen indicated self-association. An S20 value of 3.6 was obtained for the monomer, corresponding to an approximate m.w. of 50,000.

The antigen was identified as a protein with a very small amount of lipid. Data are presented on the absorption spectrum, extinction coefficient, and amino acid composition. The molecule was lacking in cysteine and tryptophan, but contained a relatively high proportion of nonpolar amino acids corresponding with a lipophilic protein. It was localized by immunofluorescence to the area surrounding the entire photoreceptor cell in a pattern indicating association with the plasma membrane. The antigen was not rhodopsin, which has been implicated as a probable antigen in the pathogenesis of EAU, but has some properties resembling a recently described photoreceptor cell retinol-binding protein tentatively implicated in the transport of vitamin A from the circulation to the retina.

Assay of the purified fraction for production of EAU in the guinea pig indicated it was highly pathogenic in the microgram range. In agreement with immunofluorescent findings, the photoreceptors were specifically destroyed after cellular infiltration of the uveal tract.
Kinetic Analysis of Target Cell Destruction by Effector T Cells
Authors: Thorn Richard M. , Henney Christopher S.
Published: December 2022

Attempts have been made to test the hypothesis that the affinity of the effector T cell's antigen receptor changes in a predictable manner with respect to the dose of antigen used to elicit effector cells and with time after antigen exposure.

Although we made no direct measurement of the affinity of the antigen receptor we have measured changes in the Kh parameter of cytolytically active lymphocyte populations. We demonstrate that this term, analogous to the Km value of enzymes, is an avidity parameter, reflecting the interaction rate of killer cells with homologous targets. We presume therefore that Kh values of killer T cells reflect the affinity of the cell's antigen receptor site.

Low doses of alloantigen elicited few killer cells of high avidity (low Kh). Killer cell avidity varied inversely with effector cell frequency, reaching minimum avidity when killer cells were present in greatest numbers. There was, however, no constant propertionality between avidity and frequency.

We suggest that these findings imply that T cell antigen receptors are heterogeneous with respect to their affinity for antigen and that clones of cells with receptors of high affinity are selected out when antigen is limiting. This selection is entirely analogous to that previously reported to operate for B cell clones and their product, serum antibody.
Requirements for Inducting Tolerance of Hapten-Specific Delayed Hypersensitivity: Epitope Density
Authors: Moon Michael M. , Redelman Doug , Wolvos T. A. , Bauer D. C.
Published: December 2022

Tolerance to hapten-specific antibody formation and delayed hypersensitivity was examined in adult rabbits. The azobenzenearsonate (ABA) or sulfonate-specific antibody response to hapten-hemocyanin immunogens was suppressed by deaggregated hapten-rabbit IgG conjugates given 21 and 14 days before challenge. High affinity antibody was preferentially suppressed. Delayed hypersensitivity to ABA-tyrosine was suppressed by deaggregated ABA-rabbit IgG conjugates injected 17 and 10 days before challenge. Conjugates with a high hapten density, ABA15–23-rabbit IgG were effective tolerogens. Conjugates with four to six ABA groups per carrier molecule were very poor tolerogens. Increasing the amount of low substituted conjugate injected did not improve tolerogenicity. It appears that a high epitope density is required for effective induction of tolerance to ABA-specific delayed hypersensitivity in the rabbit.
Immune Responses to Vaginal or Systemic Infection of BALB/c Mice with Herpes Simplex Virus Type 2
Authors: Morahan Page S. , Breinig Mary C. , McGeorge Margaret B.
Published: December 2022

The temporal relationships among the humoral and cellular immune responses were defined in BALB/c mice after vaginal or systemic infection with herpes simplex virus type 2 (HSV-2). After vaginal infection, mice showed evidence of clinical vaginitis on days 4 to 6 and HSV-2 replication was detected locally in the vaginal secretions, cervix, vagina, and uterus before the virus subsequently spread to the central nervous system. Death from encephalitis occurred between 7 and 10 days after infection. Vaginal infection was associated with significant delayed type hypersensitivity and splenic proliferative cell-mediated immune responses which appeared during the acute infection and waned by 3 weeks. There was almost no evidence of a systemic neutralizing antibody response at any time after vaginal infection. In contrast to the local vaginal infection, systemic i.v. HSV-2 infection induced a humoral response as well as the two cellular immune responses. Although both cellular immune responses appeared during the acute infection (days 6 to 14) and persisted for approximately 5 weeks, the humoral response appeared in surviving animals and persisted for at least 4 months. Thus, vaginal HSV-2 infection was associated primarily with transient cellular immune responses, whereas i.v. HSV-2 infection induced prolonged systemic humoral and cellular immune responses.
Potentiation of the Immune Response to Influenza Virus Subunit Vaccines
Authors: Webster Robert G. , Glezen W. Paul , Hannoun Claude , Laver William G.
Published: December 2022

Influenza subunit vaccines are poorly immunogenic in unprimed lower animals and man and methods were sought to potentiate the humoral response. Influenza B intact virus vaccines potentiated the antibody response of hamsters to purified vaccines containing influenza A hemagglutinin and neuraminidase subunits. The levels of antibody induced were at least as high as those induced by equivalent doses of whole virus. Similarly, intact heterologous influenza A virus vaccine (A/Victoria/3/75 [H3N2]) potentiated the antibody response of hamsters to A/NJ/76 [Hswl Nl] subunit vaccines but large doses of intact virus were required. Considerably lower doses of homologous intact A/NJ/76 [Hswl Nl] potentiated the antibody response of hamsters and sero-negative people to subunit vaccines. This suggests that future influenza subunit vaccines for use in seronegative people should contain a minimal dose of whole virus vaccine sufficient to potentiate the immune response to the subunits but insufficient to be reactogenic.

A synthetic water soluble adjuvant (N-acetyl-muramyl-L-alanyl-D-isoglutamine) was also shown to potentiate the immune response of hamsters to A/NJ/76 [Hswl Nl] influenza virus subunit vaccines.
A Splenic Requirement for the Generation of Suppressor T Cells
Authors: Sy Man-Sun , Miller Stephen D. , Kowach Helen B. , Claman Henry N.
Published: December 2022

Tolerance to contact sensitization with DNFB may be induced by DNBSO3. This specific unresponsiveness may occur via one or both of two mechanisms — production of suppressor T cells or clone inhibition. We investigated the role of the spleen in this unresponsiveness. Splenectomized mice may be tolerized by i.v. injection of DNBSO3, but they are incapable of serving as donors of lymph node cells for transfer of tolerance to normal recipients. Kinetic studies indicated that the spleen must be present at least three days after tolerization in order to permit development of a significant number of suppressor cells in the peripheral lymph nodes. We interpret these results to indicate that 1) clone inhibition does not require the spleen, 2) the generation of suppressor T cells is dependent on the presence of the spleen, and 3) it is likely that tolerogens in this system induce suppressor cells in the spleen and some of these cells or their products leave the spleen to reach the peripheral lymph nodes.
Lymphocyte Transformation Induced by Chemical Modification of Membrane Components
Authors: Beyer Carl F. , Bowers William E.
Published: December 2022

Reliable culture conditions and a valid 3H-thymidine labeling procedure were established for studies on the in vitro response of rat lymph node cells to treatment with the mitogen, sodium periodate. Six days after an initial periodate stimulation of rat lymph node cells (by which time all blasts have reverted to “secondary” lymphocytes and 3H-thymidine incorporation has declined to near background levels) the surviving cells were restimulated either directly, i.e., by retreatment of all the cells with periodate, or indirectly, i.e., in mixed cultures composed half of cells treated against with periodate, but blocked with mitomycin C (stimulator cells) and half of cells that received no retreatment (responder cells).

Both the direct and indirect restimulation responses were faster and of greater magnitude than the corresponding initial responses. The magnitude of indirect restimulation was about 36% of that of direct restimulation. Reduction of the periodate-induced aldehyde groups with sodium borohydride abolished both the direct and indirect restimulation responses. The greater magnitude of the indirect restimulation response as compared with the initial indirect response was due to an enhanced ability of the secondary lymphocytes to respond rather than to an enhanced ability to stimulate.

The responding cells in periodate-restimulated cultures were the progeny of the cells that had responded initially. Concanavalin A also restimulated at least some of the periodate progeny cells, and in addition stimulated some cells that had not responded to periodate initially. Cells from cultures initially stimulated by periodate were able to serve as indirect restimulators of cells initially stimulated by either periodate or concanavalin A. In contrast, cells initially stimulated by concanavalin A (and then treated with mitomycin C and periodate) could restimulate neither type of responder.
Neonatal Tolerance Induction across Regions of H-2 Complex
Authors: Streilein J. Wayne , Klein Jan
Published: December 2022

Regions of the H-2 complex were evaluated for their capacity to resist neonatal tolerance induction. Congenic recombinant strains and mutants were employed to study K, I, and D region disparity. It was found that tolerance could be induced to differences at each region; however, the K region of the H-2 complex is not only highly immunogenic, but markedly resistant to neonatal tolerance induction. This is especially apparent when the host is derived from B10 stocks, even though the MHC haplotypes involved are not H-2b indicating that genetic factors unlinked to the MHC clearly play an important role in determining the ease of neonatal tolerance induction.
Characterization of a Feline Leukemia Viral Cell Membrane Antigen Reactive with Feline Sera
Authors: Ruscetti Sandra K. , Parks Wade P.
Published: December 2022

Cats which have been infected with FeLV and which have recovered without disease or persistent viremia are at a low to negligible risk for subsequent development of FeLV-associated neoplasia. To evaluate the immunologic correlates of this protection, cat sera from various free-living populations were shown by immunoprecipitation of FL74 cell surface proteins to react with an 85,000 dalton cell surface protein, p85. All sera from non-viremic cats with FL74 cell membrane immunofluorescence reactivity greater than 1:32 precipitated p85. The reactivity of p85 and concomitant cell membrane reactivity could be completely removed from serum with freshly purified, undisrupted FeLV and could be blocked with specific antisera to known virion envelope glycoproteins, demonstrating that p85 contains determinants of the FeLV envelope glycoprotein. The reactivity to p85 could also be removed with FeLV-infected feline and nonfeline cells but not with cells nonproductively transformed by the feline sarcoma virus. These data strongly suggest that a major cell membrane antibody in feline sera is directed to the major FeLV envelope glycoprotein expressed on the surface of cells infected with FeLV but not FeSV. The relationship of this reactivity to the previously and presently defined anti-“FOCMA” reactivity is discussed.
Human T Lymphocyte Receptors for IgM: Reactivity with Monomeric 8S Subunit
Authors: Preud'Homme Jean-Louis , Gonnot Martine , Tsapis Andreas , Brouet Jean-Claude , Mihaesco Constantin
Published: December 2022

Up to 75% of T lymphocytes in human peripheral blood bear receptors for the Fc fragment of IgM which are easily detectable by a rosette assay (T.µ rosettes)2 (1, 2). These cells appear to belong to a subpopulation different from that of T lymphocytes with IgG Fc receptors, with distinct characteristics and functions (3, 4). IgM appears to bind to the T cell receptors by its C4 domain (5). The question of whether the receptor site on T cells binds monomeric IgM or not has important physiologic implications. In the present experiments, and in contrast to the conclusions of a previous report (6) that suggested specificity for pentameric IgM, we have found that unreduced monomeric 8S human IgM is a more effective inhibitor of T.µ rosette formation than pentameric 19S IgM. In another series of experiments, erythrocytes coated either with 8S or with 19S IgM antibodies were used for T.µ rosette formation and these experiments confirmed that monomeric IgM readily binds to the T cell receptors.
The Hypersensitiveness Following Injections of Placental Extracts
Authors: Smith George H. , Musselman L. K.
Published: December 2022

In a short note published in 1915, by d'Herelle and Géry (1) data are presented which indicate that by means of a suitably designed anaphylactic experiment it is possible to differentiate between ale and female human sera. In the experiments reporteu gumea pigs received, as a sensitizing injection, an aqueous extract of human placental tissue. After a suitable incubation period, varying from thirty-five to forty-seven days, these guinea pigs were reinjected, by the intravenous route, with human sera; some receiving male serum, other receiving female serum. The results recorded indicate that the female serum induced an acute and fatal shock whereas with the male human serum the guinea pigs failed to manifest the symptom complex of anaphylaxis.

In the more recent reviews of the literature of anaphylaxis no mention is made of these experiments nor does there appear to have been a confirmation of these results.
Immunity to Pneumococcus Produced in Rats by Feeding Them the Germ
Authors: Ross Victor
Published: December 2022

Rats which are fed the living pneumococci from 50 cc. culture per day are considerably more resistant to intraperitoneal injections of the same organism than are untreated control animals. The degree of protection is as good, although not so regular as, that previously reported as having been obtained when the tissues of animals killed by pneumococcus were fed. Rats which are fed the heat killed pneumococci (80°C., two hours) in the same quantities show a decidedly inferior degree of immunity.
Studies in Specific Hypersensitiveness
Authors: Grove Ella F.
Published: December 2022

The “epidemic” form of bronchial asthma described by G. Ancona in Florence has been studied there with respect to the nature of the skin reactivity, and also in order to see whether the blood of the affected individuals contains atopic reagins. The cutaneous reaction was found to be different from that of atopic hypersensitiveness; (a) because it is quite inconstant and (b) because it is exhibited upon surface application of the excitant. Sensitizing bodies could not be demonstrated in the blood of either of the 2 sensitive individuals presenting a markedly positive skin reaction. The “epidemic” form of asthma must be placed in a special category, since it differs from the inherited form and also from the “non-sensitive” group of Cooke.
Response of Orally Immunized Rats to a Second Injection of Pneumococcus and the Minimum Duration of Immunity
Authors: Ross Victor
Published: December 2022

Introduction. The results obtained in the immunization of rats against intraperitoneal injections of pneumococcus, Type I, by feeding either the tissues of animals killed by that organism or by feeding the living organisms, have been reported elsewhere (1, 2). It has been demonstrated that rats so treated possess a degree of immunity which enables them to tolerate an intraperitoneal injection of 1000 or more times the dose which kills controls. Most of the animals which thus survived were kept and tested a second time. The interval of time elapsing between the first and second tests varied from one to four months. The object was to learn whether a second injection, approximately equal to the first, can be tolerated and if so how long after the first. The results of such an experiment do not indicate how long the immunity originally conferred lasts.
Studies in Microbic Heredity
Authors: Mellon Ralph R. , Jost Elizabeth L.
Published: December 2022

Introduction. The inagglutinability of freshly isolated typhoid bacilli is a well established fact, but despite the many explanations that have been suggested for the phenomenon, according to Zinsser (1916) “no satisfactory solution has been found.” From his review of the experimental evidence Zinsser takes the position—which is now the conventional one—that contact of the organisms with immune sera or exudates is a prerequisite for the acquisition of inagglutinability. Substantiating this point of view is the fact that typhoid organisms isolated from the stools of patients are rarely inagglutinable while those isolated from the blood are commonly so.

In any event, such changes of state with these organisms are conventionally referred to metabolic or physico-chemical influences. Hereditary considerations have been ignored or supposed to be contravened by the evidence. It is our purpose to submit evidence showing that the factors producing inagglutinable strains from agglutinable ones, or vice versa, have nothing specifically to do with immune sera or exudates since they will occur regularly in their absence.
Studies in Microbic Heredity
Authors: Mellon Ralph R.
Published: December 2022

Introduction. The large number of contributions in recent years to the subject of bacterial variability, especially in its bearing on the specificity of serologic reactions attests the serious consideration that the subject deserves. As one who has had an abiding interest in the field of bacterial genetics for many years I believe these practical applications of variability will yield most when correlated with the newer knowledge of the general biology of bacteria.

Krumwiede, Cooper and Provost (1925) while devoting generous space to the subject as it affects the application of the agglutinin-absorption test consider it in a singularly detached fashion. While such treatment is perhaps adequate for their purpose it cannot but be handicapped by virtue of the proscriptions thrown about the interpretations.

From the earliest days of bacteriology the doctrines of monomorphism in practically an absolute sense have underlaid all of our knowledge of their biology. Division by tranverse fission, and the formation of heat resisting spores practically told the story of the life history of bacteria.
The Sensitization of Pigeons to Foreign Proteins
Authors: Gahringer John Edward
Published: December 2022

The pigeon is readily sensitized to a foreign protein as here demonstrated by the use of dog's serum. When the most favorable sensitizing and critical doses are used, a demonstrable induced sensitiveness occurs on the fourth day, increases rapidly to the tenth day, and reaches a maximum by the twentieth day. It then decreases gradually to disappear between the sixtieth and seventieth days. When single or multiple shock reactions are induced in the pigeon, each and every reaction is followed by a definite period of insensitiveness. The primary change in blood coagulability during anaphylactic shock is an increase in coagulability, to which a decrease in coagulability is always secondary.
Improved Procedures for the Fractionation and in Vitro Stimulation of Hapten-Specific B Lymphocytes
Authors: Nossal G. J. V. , Pike Beverley L.
Published: December 2022

Spleen cells from unimmunized adult CBA mice were subjected to fractionation procedures dependent on their capacity to adhere to monolayers or erythrocytes on which the haptenic determinant NIP was exposed. Subsequent to removal of adherent antigen, in vitro analysis for anti-NIP precursors was performed by culture at limiting dilution in a microculture system with thymus cells as a “filler” population and by using the “T-independent” antigen NIP-POL to induce antibody formation. Cultures were harvested and assayed for anti-NIP-specific PFC after 3 to 7 days and the frequency of clonable anti-NIP precursor B cells determined by Poisson analysis.

Whereas one cycle of NIP-gelatin fractionation produced a population in which the average frequency of anti-NIP precursors was about 0.04, three successive cycles (two of NIP-gelatin fractionation and one of NIP-SRBC rosetting) raised this frequency to 0.28. The fact that one cell in three and one-half from a “virgin” population could make an antibody-forming clone in vitro with specificity for the hapten used in preparing the fractionated population should be helpful for many detailed studies of B cell interactions with antigen. Bearing in mind the technical limitations of lymphocyte culture and the possibility of functional heterogeneity among B lymphocytes of a given specificity, one may assume that it may not be easy to surpass this cloning efficiency by antigen fractionation alone.

Cells obtained from one cycle NIP-gelatin fractionation of neonatal germfree or SPF spleen, or adult bone marrow, behaved in vitro essentially as cells obtained by one cycle fractionation of adult spleen, strongly suggesting that the technique is applicable to virgin cell populations. Some cultures harvested later than the standard 3 to 4 day peak of direct plaque formation showed clones consisting chiefly or solely of enhancable plaques. These may have been IgG-producing clones, raising the possibility that T helper cells had been activated in vitro by the carrier POL.
The Identification of Six Mouse Lymphocyte Subpopulations by Their Natural Binding of Bacteria
Authors: Mayer Eugene P. , Chen Wen-Yuan , Dray Sheldon , Teodorescu Marius
Published: December 2022

The natural adherence of eight strains of bacteria to mouse spleen cells is described. The bacteria used were: Arizona hinshawii, Brucella abortus, Brucella melitensis, Corynebacterium xerosis, three strains of Escherichia coli (E. coli-2, E. coli-3 and E. coli-4), and Pasteurella pestis. A strain of E. coli that did not bind naturally to spleen cells was chemically coated with anti-mouse Ig antibodies (anti-Ig Ab-E. coli) and used to identify cells with surface Ig, i.e., Ig+ cells (B cells). Cells that lacked detectable surface Ig (Ig- cells) were considered to be primarily T cells. By mixing anti-Ig Ab-E. coli and another bacteria with the lymphocytes, we found that some of the bacteria bound to either Ig+ or Ig- cell subsets and some bound to both Ig+ and Ig- cell subsets. One strain of bacteria (B. melitensis) bound to essentially all of the Ig+ cells and none of the Ig- cells. By labeling the lymphocytes with various combinations of two bacteria, we identified three Ig+ (B cell) and three Ig- (presumably T cell) lymphocyte subpopulations. B1 cells bound B. melitensis, B. abortus, and C. xerosis; B2 cells bound B. melitensis, A. hinshawii, C. xerosis, E. coli-2, and E. coli-4; B3 cells bound B. melitensis, P. pestis, and E. coli-2, T1 cells bound C. xerosis, E. coli-2, and E. coli-3; T2 cells bound E. coli-3 and E. coli-4. T3 cells did not bind any of the bacteria. Whereas B. melitensis, C. xerosis, E. coli-2, E. coli-3, and E. coli-4 adhered to more than one subset of lymphocytes, B. abortus, A. hinshawii, and P. pestis adhered to only a single subset—B1, B2, and B3 cells, respectively. The use of the natural adherence of bacteria to lymphocytes provides a simple method for identifying lymphocyte subpopulations and may facilitate the elucidation of the roles that lymphocyte subsets play in immune phenomena.
Antigenic Modulation in Vitro.
Authors: Stackpole Christopher W. , Jacobson Janet B. , Galuska Stefan
Published: December 2022

The acquisition of resistance by TL antibody-sensitized mouse RADA1 leukemia cells and A/J thymocytes to cytolysis in the presence of fresh TL antiserum and guinea pig C (TL antigenic modulation) required a heat-labile mouse serum factor or factors. Most mouse strains had high levels of serum-modulating activity, but the B6 strain was extremely low, and the AKR/J strain moderately low, in activity. The modulating capacity of mouse serum was also destroyed by treatment with zymosan, an immune complex, and cobra venom factor, and was partially restored to heated serum by freeze-thawing.

Human C component C3, and to a lesser extent C4, promoted modulation of cells presentitized with heated TL antiserum and cobra venom factor-treated normal serum. Similar sensitivity of modulating activity of human C3 and of mouse serum to temperatures below 37°C indicated that an analogous mouse C component, mouse C3, was required for modulation. Successful modulation by C2-deficient human serum and susceptibility of mouse serum activity to zymosan, immune complex, and cobra venom factor treatment indicated involvement of the alternative pathway of C activation. All modulating activity in mouse serum and in human C3 preparations could be absorbed onto and eluted from RADA1 cells and thymocytes. Immunofluorescence analysis indicated specific binding of mouse or human C3 to the cell surface only under conditions promoting modulation.

Modulating activity of human C3, unlike that of mouse serum, was not destroyed by heating, and modulation was achieved with the IgG fraction of TL antiserum and heated human C3, suggesting a contribution of factor B-like, C3-cleaving activity by the cells, resulting in deposition of C3 on the cell surface. Intercalation of C3 into aggregated TL antigen-antibody complexes may be required to achieve modulation.
Specific Suppression of the Immune Response by a Factor Obtained from Spleen Cells of Mice Tolerant to Human γ-Globulin
Authors: Taniguchi Masaru , Miller Jacques F. A. P.
Published: December 2022

An antigen-specific suppressive factor was extracted from spleen cells of mice made tolerant by injection of deaggregated human γ-globulin (HGG). The active material could be prepared from T cells, obtained by passaging spleen cells through an anti-immunoglobulin column, although not from cells adherent to the column nor from spleen cells pretreated with anti-Thy-1 serum and C. This factor was antigen-specific since it was retained on immunoadsorbents containing HGG, but not on columns coated with antibody to HGG or with irrelevant antigens. Despite its specificity for antigen it did not bear any classical immunoglobulin determinants. Its m.w. ranged between 30,000 and 55,000 daltons. It was a product of the I region of the major histocompatibility complex since it carried Ia determinants. The properties of this factor are very similar to those reported elsewhere for suppressive factors obtained from primed T cells, cells from nonresponder mice, and allotypespecific cells. This suggests the existence of a major class of immunoregulatory molecules, nonimmunoglobulin in nature, and responsible for the mediation of antigen-specific T cell-dependent suppression.
Suppression of Natural Killer Cell Cytotoxicity by Splenocytes from Corynebacterium Parvum-Injected, Bone Marrow-Tolerant, and Infant Mice
Authors: Savary Cherylyn A. , Lotzova Eva
Published: December 2022

Natural killer (NK) cell cytotoxicity to YAC-1 lymphoma was investigated in mice tolerant to bone marrow grafts (BM-tolerant), Corynebacterium parvum- (C. parvum) treated mice, and infant mice. Also the comparison was made between the NK cells and the hemopoietic-resistance effector (HR-E) cells. It was found that the BM-tolerant mice and C. parvum-treated mice showed either no or markedly decreased NK cell cytotoxicity. These mice were also nonresponders to bone marrow grafts in vivo. The lack of or decreased reactivity was apparently caused by the regulatory cell activities of the suppressor cell since the splenocytes from C. parvum-treated and BM-tolerant mice suppressed significantly the cytotoxic activities of otherwise fully functional NK cells. Similar suppressive effect on NK cells was mounted by splenocytes from infant mice, indicating again the suppressor cell regulation of NK cell cytotoxicity.
C57BL/10/CR Mice: Nonresponders to Activation by the Lipid a Moiety of Bacterial Lipopolysaccharide
Authors: McAdam Keith P. W. J. , Ryan John L.
Published: December 2022

C57BL/10/CR mice do not respond to the lipid A moiety of LPS. This defect was demonstrated in vivo by a decreased production of the acute phase serum amyloid protein SAA. In addition, the defect was demonstrated in vitro by using cultures of spleen cells and peritoneal cells. No mitogenesis of spleen cells or enhanced glucose utilization by either spleen cells or peritoneal cells was observed when the cells were stimulated by lipid A or phenol-extracted Escherichia coli K235 LPS. The response of these mice to PHA, Con A, Poly I:C, 8BrcGMP, and butanol extracted E. coli K235 LPS was normal. Thus, the inability of lipid A to stimulate B lymphocyte mitogenesis and activate peritoneal cells in vitro may correlate with its inability to induce the acute phase SAA in vivo. B10/CR mice represent another strain, similar to the C3H/HeJ, which is nonresponsive to lipid A and should be useful in elucidating the mechanism by which bacterial LPS activates cells.
Defective Tumoricidal Capacity of Macrophages from C3H/HeJ Mice
Authors: Ruco Luigi P. , Meltzer Monte S.
Published: December 2022

Peritoneal macrophages from C3H/HeN mice treated i.p. with T cell mitogens or viable BCG organisms were cytotoxic to syngeneic tumor cells in vitro. Macrophages from endotoxin-unresponsive C3H/HeJ mice treated with BCG or T cell mitogens, however, were not tumoricidal. Furthermore, unlike cells from C3H/HeN mice, macrophages from C3H/HeJ mice could not be activated for tumor cytotoxicity after in vitro treatment with bacterial endotoxins or with lymphokine-rich supernatants. The subnormal induction of cytotoxic macrophages after in vitro or in vivo treatments in C3H/HeJ mice appears to be a highly selective defect. Macrophage responses (yield, phagocytosis, or peroxidase staining) in inflammatory exudates induced by BCG, T cell mitogens, or heterologous serum in C3H/HeJ or C3H/HeN mice were identical. C3H/HeJ macrophages also responded normally in vitro to chemotactic lymphokines. Thus, C3H/HeJ macrophages possess a profound and selective defect in tumoricidal capacity. This defect was not dependent upon exogenous endotoxins. Defective macrophage cytotoxic responses may reflect non-LPS related functions regulated by the LPS gene.
Mediated Cytotoxicity in Murine Schistosomiasis
Authors: Coulis Paul A. , Lewert Robert M. , Fitch Frank W.
Published: December 2022

An impairment of the capacity to generate alloantigenspecific cytotoxic T lymphocytes (CTL) was observed in mixed lymphocyte cultures (MLC) established with spleen cells from mice infected with Schistosoma mansoni. This impairment, which was observed as early as the eighth week of infection, could be abrogated by the fractionation of spleen cell suspensions by the carbonyl iron/magnet method prior to the establishment of MLC. Cocultivation of normal spleen cells with increasing numbers of splenocytes from S. mansoni-infected syngeneic mice resulted in a dosage-dependent suppression of CTL generation. This “infectious suppression” was not sensitive to antiserum against mouse thymic lymphocyte antigen (MTLA).

The present studies suggest the role of a macrophage rather than a T cell as the suppressor cell in this model of cell-mediated immunity in schistosome-infected mice.