bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Distinct Populations of Suppressor Cells in the Spleens of Mice Bearing Methylcholanthrene-Induced Tumors
Authors: Pope B. L. , Whitney R. B. , Levy J. G. 
Published: December 2022

Abstract
The suppressor cells found in the spleens of mice bearing advanced tumors could be divided into two different populations by centrifugation on Hypaque-Ficoll of specific gravity 1.08. The cells in the light fraction suppressed the in vitro PFC response to SRBC and DNP-LPS. They appeared to be of the macrophage/monocyte line since they were adherent to plastic and nylon wool but were not removed by anti-BA-ϑ serum plus complement (C). They did not require DNA synthesis for activity since they were not inactivated by mitomycin C. The cells in the dense fraction suppressed only the response to SRBC. They may have been T cells since they were not adherent to plastic or nylon wool and their activity was reduced by treatment with anti-BA-ϑ serum plus C. They did require DNA synthesis since their activity was removed by treatment with mitomycin C. Suppression of normal lymphocyte function could be affected when splenic suppressor cells were separated from the normal population by a cell-impermeable membrane. Suppression occurred when the two populations were separated by a 0.8-µ Nuclepore membrane or by regular dialysis tubing but not when low porosity dialysis buting (m.w. &lt;3,500 retained) was used. The suppressor cell in this system was nonadherent to plastic, partially adherent to nylon-wool, not removed by carbonyl iron and magnet, and pelletted to the bottom of a Hypaque-Ficoll gradient.
Cell Types Involved in Cytotoxicity Induced by Heated Cells and Inhibition of This Cytotoxicity by Anti-Human B Cell Sera
Authors: Kasakura Shinpei 
Published: December 2022

Abstract
We have studied the induction of cytotoxic activity in human peripheral blood lymphocytes by heated allogeneic cells. By separating T and B cells from the responder and stimulator cell populations we found that cytotoxic cells are generated in responder T cell populations by both T and the B stimulator cells.
Rabbit antisera to a membrane glycoprotein complex (33,000 and 27,000 m.w. by SDS-gel electrophoresis) isolated from a human B cell line were utilized to explore further the nature of the effector cells in this type of cytotoxicity. This antiserum, present during the 6-day-culture period, blocked generation of cytotoxic effector cells. Depletion of cells bearing the B cell antigen from the responder cell population by anti-B cell serum and complement (C) eliminated cytotoxicity. Furthermore, heated cell-induced cytotoxicity was blocked by simply pretreating the responder or the stimulator cell populations with anti-B cell serum in the absence of C. Apparently the human lymphocyte that functions as the effector cell in heated cell-induced cytotoxicity bears the Ia-like antigen that might be important in triggering this type of cytotoxicity.
Isolation and Analysis of H-2 and Ia Alloantigens from Wild Mouse Strains
Authors: Cullen Susan E. , Hansen Ted H. , Klein Jan 
Published: December 2022

Abstract
Immunoprecipitation and SDS-PAGE analysis were used to examine H-2 and Ia antigens from mouse strains with wild-derived MHC haplotypes. Antisera raised against the wild-derived strains contained anti-H-2 and anti-Ia antibodies which precipitated antigen molecules readily distinguishable by a single assay procedure. The antibodies to wild strains were cross-reactive with standard laboratory haplotypes. Evidence supporting the similar genetic organization of wild and standard haplotypes was found, including isolation of separate H-2K and H-2D molecules from a wild-derived strain, and isolation of two separate Ia molecules from a wild-derived strain.
Light Chain Diversity of Murine Anti-Streptococcal Antibodies: IgCH-Linked Effects on L Chain Expression
Authors: Perlmutter Roger M. , Briles David E. , Greve Jeffrey M. , Davie Joseph M. 
Published: December 2022

Abstract
L chains derived from anti-group A streptococcal carbohydrate antibodies raised in A/J, BALB/cJ, C57BL/6J, CB-20, BAB-14, and CAL-20 mice were examined by isoelectric focusing. Multiple strain-associated differences in the degree and frequency of expression of particular L chain spectrotypes were observed. Analysis of L chain-focusing patterns in allotype-congenic mice revealed that IgCH-linked genes can have profound effects on the L chain phenotypes expressed by strains with identical L chain genotypes. Lastly, the overall spectrotypic diversity of L chains from anti-GAC antibodies appears to be less extensive than the diversity of the antibodies from which these L chains derive, documented by similar techniques. These results are interpreted in light of the significance of combinatorial diversity in generating antibody heterogeneity.
Identification and Characterization of a New Subset of Rat T Lymphocytes
Authors: Kierszenbaum Felipe , Budzko Delia B. 
Published: December 2022

Abstract
Subpopulations of rat T lymphocytes described in this paper are defined by their susceptibility to the selective cytotoxic effects of normal guinea pig serum (GPS). These cells were present in relatively large proportions in the bone marrow and thymus and in very small percentages in the spleen and lymph nodes. Tissue distribution of GPS-sensitive lymphocytes was similar in three inbred strains and, therefore, was characteristic of the species rather than a single strain. Adherent peritoneal cells were largely insensitive to GPS. The partial cytotoxicity of GPS on rat lymphoid cells contrasted with the indiscriminate killing capacity of normal sera from humans, rabbits, and chickens, which affected over 98% of the cells regardless of organ location. Variations of the number of cells used in otherwise identical GPS-cytotoxicity assays did not significantly alter the proportion of either thymus or bone marrow cells killed. This suggests a selective sensitivity by discrete subclasses of lymphocytes present in these organs. GPS-sensitive lymphocytes occurred in rat bone marrow from birth and constituted 30 to 50% of the nucleated cells. The percentage of these cells decreased after 5 weeks of age to 15 to 30%, with most value being around 20%. Cells susceptible to GPS cytotoxicity were absent in the thymus of 35-day-old or younger rats but were readily detectable in 8-week-old animals, suggesting that GPS-reactivity defines a thymus cell surface-differentiation component. The subset of the thymus cell expressing this marker was essential for responsiveness to either PHA or Con A. Prior killing of bone marrow cells with GPS left no cells to be killed specifically by rabbit anti-rat Thy 1 IgG plus complement (C) free of nonspecific cytotoxicity. Initial killing of bone marrow cells with anti-Thy 1 and C consistently eliminated the GPS-sensitive cells. These results indicate that in the rat bone marrow, unlike in the thymus, GPS-sensitive and Thy 1-bearing lymphocytes constitute the same cell subpopulation. GPS is capable of “recognizing” and killing subpopulations of rat T lymphocytes, a property that can be used to characterize further these cells on a functional basis.
The Control of Autoreactivity
Authors: Osband Michael , Parkman Robertson 
Published: December 2022

Abstract
To determine if autocytotoxic lymphocytes were naturally occurring in murine spleens, C57BL/6 spleen cells were fractionated on discontinuous BSA gradients. Autocytotoxicity was assessed in vitro (cytotoxicity of C57BL/6 fibroblasts) and in vivo (splenomegaly and popliteal node enlargement in C57BL/6 mice). A medium density subpopulation of lymphocytes was shown to be autocytotoxic and to be similar to autoreactive lymphocytes produced by the in vitro “sensitization” of splenic lymphocytes on syngeneic fibroblasts monolayers. The naturally occurring autocytotoxic lymphocytes express no detectable Θ antigen, did not adhere to nylon, but did have an Fc receptor. In recombination experiments, BSA-fractionated lymphocytes were incubated with autocytotoxic and “sensitized” lymphocytes. A light density subpopulation was shown to suppress both autoreactive lymphocyte subpopulations at a 1:50 ratio. The suppressor cells were nylon nonadherent T lymphocytes. The lack of autoreactivity of unfractionated murine spleen cells is due to the concomitant presence of autocytotoxic and suppressor lymphocytes. If suppressor lymphocytes are selectively removed in vitro, the reactivity of autocytotoxic lymphocytes can be detected.
IgE-B Cell-Generating Factor from Lymph Node Cells of Rats Infected with Nippostrongylus Brasiliensis
Authors: Urban Joseph F. , Ishizaka Kimishige 
Published: December 2022

Abstract
Cell-free culture supernatants (CFS) of mesenteric lymph node cells from Nippostrongylus brasiliensis-infected rats specifically increase the proportion of IgE-bearing cells in normal rat bone marrow cultures without changing the proportion of IgM-bearing cells and IgG2a-bearing cells. Virtually all of the IgE-bearing cells appearing in the culture carried IgM determinants on their surface. Precursors of IgE-bearing cells in normal bone marrow cells were removed by depletion of immunoglobulin-bearing cells. These findings indicate that IgE-B cell-generating factor converts IgM-bearing virgin B cells to IgM-IgE double bearing cells. Pretreatment of normal bone marrow cells with mitomycin C failed to inhibit the generation of IgE-bearing cells by the soluble factor. Indeed, most of IgE-bearing cells generated in cultures of mitomycin C-treated bone marrow cells did not contain 3H-thymidine, which was present during the entire culture period. It appears that DNA synthesis is not required for the differentiation of IgM-bearing cells to IgE-IgM double bearing cells. However, the appearance of IgE-bearing cells in cultures of normal bone marrow cells by CFS was abated by 0.5 µg/ml of actinomycin D or by pretreatment of the cells with pactamyicn. These findings suggest that the observed differentiation involves some process dependent on transcription of DNA and protein synthesis.
The Induction of Hapten-Specific Immunologic Tolerance and Immunity in B Lymphocytes
Authors: Fidler John M. 
Published: December 2022

Abstract
In vivo administration of trinitrobenzenesulfonic acid (TNBS) induces a state of immunologic tolerance to the trinitrophenyl (TNP) hapten in the bone marrow-derived (bursal equivalent, B) lymphocytes of mice. An in vitro culture system utilized to generate an antibody forming cell (AFC) response was characterized and used to evaluate the unresponsive state. The tolerance induced by TNBS injection was TNP-specific and dose-dependent, and was present in response to both the thymic-derived (T) cell independent (TI) antigen TNP-lipopolysaccharide (TNP-LPS) and a T cell dependent (TD) form of TNP (TNP-sheep erythrocytes, TNP-SRC). Unresponsiveness persisted for over 8 weeks in response to either antigen.
Experiments were conducted to determine the mechanism of TNBS-induced immunologic tolerance with emphasis upon differentiation between B cell deletion and blockade of surface immunoglobulin (sIg) receptors by tolerogen. Tolerant and normal spleen cells responded independently to TNP-LPS when co-cultured, indicating that the observed unresponsiveness in TNBS-treated spleen cells was not due to suppression of TNP-specific B lymphocytes by other cells in the preparation. Used at polyclonal B cell-activating concentrations, TNP-LPS did not reverse the tolerant state. Additionally, unconjugated LPS in either serum-containing or serum-free cultures did not break tolerance. Because polyclonal B cell activators do not act in triggering through sIg receptors, the failure of a polyclonal stimulator to reverse the tolerant state suggests that blockade of TNP-specific surface receptors is not the mechanism of tolerance. Tolerant spleen cells did not reduce the number of TNP-specific plaque forming cells (PFC) produced upon stimulation of normal cells by a wide range of LPS doses, supporting the conclusion that suppressive cells or factors are absent. Antigen-free incubation of tolerant spleen cells for 24 hr and washing at 4°C did not abrogate the unresponsive state when followed by challenge with either TNP-LPS or TNP-SRC. Washing at elevated temperatures after pre-culturing in order to avoid possible reassociation of sIg-bound TNP conjugates was equally unsuccessful in reversing tolerance. Thus, antigen-free precultivation where unblocking or turnover and resynthesis of sIg receptors should have taken place yielded no evidence supporting receptor blockade as the basis of TNBS-induced tolerance. Treatment with the proteolytic enzyme pronase, in order to strip potential tolerogen from the cell surface, failed to reverse the unresponsive state. Incubation with anti-TNP or anti-Ig antibody under conditions designed to allow capping and removal of surface-bound trinitrophenylated moieties or sIg-bound tolerogen also revealed a stable tolerant state.
These results and evidence presented previously support the conclusion that TNBS induces tolerance in vivo through a deletion of TNP-specific B lymphocytes.
Dextran Alters Induction of Cell-Mediated Hypersensitivity
Authors: Alevy Y. G. , Battisto J. R. 
Published: December 2022

Abstract
Administering dextran to 6- to 8-week-old CBA/J mice just before applying the initial sensitizing dose of a hapten caused induction of heightened delayed-type responsivity to the hapten. Measured by an isotope localization method, the cell-mediated hypersensitivity engendered by a hapten, picryl chloride, was twice as great in animals receiving dextran than in control animals given the saline vehicle. Optimal enhancement was achieved when dextran administration preceded hapten by 2 hr. Furthermore, the augmentation was observed at the first test after the initial sensitization period but not after repetitive dermal applications of the hapten had been made over a prolonged time interval. In the latter instance diminution of sensitivity was observed.
Washed lymphoid cells, taken from animals 2 hr after treatment with dextran, transferred to x-irradiated syngeneic recipient animals the heightened capacity to become sensitized. Such lymphoid cells retained the ability to transfer the heightened capacity to become sensitized despite removal of macrophages by plastic-adherence.
Although dextran is known to cause murine T cells to release factors that increase responses of other T cells to mitogens, it is not known whether dextran affects that subpopulation of T cells directly mediating contact sensitivity or whether its action is upon a separate subpopulation of T cells concerned with immuno-regulation.
Suppressor T Cell Mechanisms in Contact Sensitivity
Authors: Miller Stephen D. , Sy Man-Sun , Claman Henry N. 
Published: December 2022

Abstract
We investigated mechanisms of suppression of contact sensitivity to DNFB in mice. In particular, we studied the suppression produced by suppressor T cells which had been induced by injection of syngeneic DNP-modified lymphoid cells (syninduced Ts). Syninduced Ts were found by several criteria to inhibit the efferent limb of sensitivity by inhibiting the expression of LN cells from DNFB-sensitized animals. First, syninduced Ts can suppress previously sensitized recipients in an antigen-specific manner. Second, co-transferred syninduced Ts could block the passive transfer of contact sensitivity by DNFB-immune LN cells given to normal recipients. This inhibition was shown to be dose dependent, antigen specific, and non-MHC restricted. Third, in reverse transfers of sensitized cells into tolerant recipients, only those recipients containing active syninduced Ts could inhibit the expression of sensitivity by the passively transferred immune T cells. In contrast, syninduced Ts were incapable of inhibiting the afferent limb of the response as assessed by the normal, post-sensitization DNA synthetic response of draining LN cells in Ts recipient mice. Syninduced Ts were not inhibitable by prior treatment with anti-TNP antiserum, indicating a lack of surface-associated tolerogen. The locus of suppression was most clearly shown in experiments where mice received syninduced Ts at the same time they were sensitized. These mice were themselves unresponsive, but did contain immune lymphoid cells able to express contact sensitivity after transfer to normal recipients followed by DNFB challenge. The data suggest that the suppressive environment allows the development of a normal complement of DNFB-specific immune T cells, but inhibits the expression of this sensitivity. The data are discussed in terms of current models of suppression, and are compared with mechanisms of suppression in other contact sensitivity models.
Loss of Self-Tolerance to Single-Stranded Deoxribonucleic Acid (sDNA) in Vitro
Authors: Roder John C. , Bell David A. , Singhal Sharwan K. 
Published: December 2022

Abstract
The spleens of many normal and autoimmune-susceptible strains of mice mount a specific, IgM, anti-sDNA plaque-forming cell (PFC) response in vitro in the absence of an exogenous source of antigen. This response was not related solely to levels of xenotropic or ecotropic virus and was generated from a small number of precursor cells capable of binding sDNA. Small numbers of anti-sDNA PFC were also apparent in serum-free medium and the response of low-responder strains could be augmented with pokeweed mitogen. T cells and macrophages were not essential and cell division was required early in culture to obtain a peak response on day 5. These results suggest that autoantigen-sensitive cells may escape normal regulatory mechanisms in vitro and differentiate into clones of autoantibody secreting cells.
Oxygen Immunosuppression: Modification of Experimental Allergic Encephalomyelitis in Rodents
Authors: Warren Joel , Sacksteder Miriam R. , Thuning Claire Ann 
Published: December 2022

Abstract
Using protocols that incorporated double blind examination of animals sensitized to CNS antigen, we confirmed and amplified earlier findings of the complete suppression of EAE in rodents by hyperbaric oxygen. The effects of O2 were related to the gas pressure and duration of treatment. The development of paralytic disease was prevented for 34 days after sensitization (the longest interval studied). Compressed air or normobaric O2 administered under similar conditions did not modify the course of illness. Within 7 to 10 days after the discontinuance of oxygen therapy the majority of treated guinea pigs developed typical signs of EAE with characteristic lesions in the CNS. The relapses occurred sooner in the Lewis rat. The development of the delayed hypersensitivity reaction to myelin basic protein and to tuberculin is also suppressed by O2 therapy indicating that its effects upon autoimmune encephalomyelitis involves fundamental alterations of the cellular components of the immune response, some or all of which are reversible.
Histamine Release Due to Bivalent Penicilloyl Haptens Control by the Number of Cross-Linked IgE Antibodies on the Basophil Plasma Membrane
Authors: Dembo Micah , Goldstein Byron , Sobotka Anne K. , Lichtenstein Lawrence M. 
Published: December 2022

Abstract
We describe the characteristics of in vitro histamine release from human basophils passively sensitized with serum from a penicillin-allergic individual. The histamine release is induced by a synthetic bivalent hapten, bis benzylpenicilloyl 1,6 diaminohexane (BPO)2. We present data on the effect of a monovalent hapten, benzylpenicilloyl formyl-l-lysine (BPO)1, on the histamine release. We also examine how histamine release depends on the concentration of serum used for passive sensitization, the source of cells used for passive sensitization, and the time allowed for histamine release.
We interpret these experiments in terms of a theory of equilibrium binding of bivalent haptens to cell surface antibody that is presented in the previous paper. The results are consistent with the idea that the amount of histamine release is controlled by the number of cross-linked IgE molecules on the cell surface. In particular, the histamine dose-response curve rises because cross-links rise, has a maximum because the cross-links are a maximum, and falls because the cross-links fall.
Regulation of the Autoimmune Plaque-Forming Cell Response to Single-Strand DNA (sDNA) in Vitro
Authors: Roder John C. , Bell David A. , Singhal Sharwan K. 
Published: December 2022

Abstract
We have shown that young autoimmune and normal strain mice possess autoantigen-sensitive cells potentially capable of producing anti-sDNA autoantibody in the absence of normal regulatory mechanisms in vitro. In certain strains such as B/W mice, these regulatory mechanisms presumably break down with increasing age, and autoimmunity develops. These regulatory mechanisms might consist of sDNA, T cells, or some combination of these since both of these agents suppressed the anti-sDNA PFC response in vitro. The sDNA may have inhibited PFC development by a receptor blockade mechanism since i) spleen cells pulsed with sDNA for short periods and then washed were suppressed after 5 days of culture; ii) treatment of these blocked cells with trypsin and DNase I restored the anti-sDNA response; iii) the PFC remaining in partially blocked cultures were of lower avidity than PFC in unblocked cultures; and iv) the target of sDNA may be a B cell.
Thymocytes and splenic T cells suppressed the anti-sDNA response but not the anti-SRBC response in vitro in a dose-dependent manner. The suppressive capacity of thymus cells did not decline with age in B/W mice. In addition, thymus cells activated by competing foreign antigens could also suppress the anti-sDNA response. The relationship between these modes of regulating autoreactivity remains to be investigated.
Effect of a Synthetic Adjuvant on the Induction of Primary Immune Responses in T Cell-Depleted Spleen Cultures
Authors: Watson James , Whitlock Cheryl 
Published: December 2022

Abstract
N-acetylmuramyl-l-alanyl-d-isoglutamine (muramyl dipeptide) stimulates in vitro primary immune responses to SRBC in T cell-depleted (nude) spleen cultures. The stimulation of immune responses by muramyl peptide was antigen dependent. A microculture system was used to compare the T cell-replacing activities of several structural analogues of muramyl dipeptide and to compare the activity of muramyl dipeptide to helper T cells. In a limiting dilution analysis with excess helper T cells or muramyl dipeptide, the frequency of B cell precursors that respond to SRBC was similar, ranging from 1.5 to 5 × 10-5. Decreasing the cell density in microcultures did not affect the efficiency of B cell precursor responses in the presence of muramyl dipeptide. Muramyl dipeptide was examined for mitogenic activity in spleen cell cultures. In serum-free medium, muramyl dipeptide stimulates slight (3-fold) increases in DNA synthetic activity. In medium supplemented with 5 to 20% fetal calf serum, muramyl dipeptide showed no significant mitogenic activity. There are a number of possible explanations for the T cell-replacing activity of muramyl dipeptide. The most likely is that muramyl dipeptide interacts directly with B cells to mimic the helper T cell signal in the inductive stimulus.