bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage-Mediated in Vitro Sensitization of Lymphocytes
Authors: Treves Abraham J. , Declève Alain , Lieberman Miriam , Feldman Michael , Kaplan Henry S. 
Published: December 2022

Abstract
Unprimed lymphocytes were sensitized in vitro by incubating them with syngeneic macrophages that had been fed with viral or cellular antigens. The sensitized lymphocytes were tested for their cytotoxic activity against virus-infected and noninfected fibroblasts. The antigenic preparations used for priming the macrophages were either tumor cell-free extracts or supernatants from virus productive cells. Cell-free extracts from the productive RadLV-induced lymphoma cells or the nonproductive radiation-induced lymphoma cells were immunogenic when presented to lymphocytes by macrophages. In contrast, cell-free extracts from normal thymocytes were much less immunogenic, suggesting that the presence of viral associated antigens (VAA) can selectively be detected on lymphoma cells by this assay. Fibroblastic cell lines but not primary fibroblasts were also susceptible to the cytotoxic lymphocytes induced by RadLV-fed macrophages. Primary fibroblasts became susceptible to the sensitized lymphocytes either after infection with the corresponding virus, or if not infected, after several passages in vitro, suggesting that neo-antigens cross-reacting with viral antigens appear during sub-culturing of fibroblasts in vitro. This system makes it possible to detect VAA either as immunogens when presented to lymphocytes by macrophages, or as targets for cytotoxic lymphocytes.
Leukocyte-Adherence Inhibition: A Specific Assay of Cell-Mediated Immunity Dependent on Lymphokine-Mediated Collaboration between T Lymphocytes
Authors: Powell A. E. , Sloss A. M. , Smith R. N. 
Published: December 2022

Abstract
The leukocyte-adherence inhibition (LAI) assay was studied to determine its immunologic relevance and identify the cell populations on which it depends. Two systems were employed: peripheral blood leukocytes from humans immunized with KLH, and lymph node cells from rats immunized with DNP-BGG. In both cases, LAI responses appeared about 3 to 4 days after immunization, reached a peak about 3 to 4 weeks later, and diminished thereafter. Reimmunization resulted in a booster-like response. LAI analysis in both systems showed dose-response dependency. Responses could be elicited only with the immunizing antigen. Virtual depletion of phagocytic cells had no effect on the response. E-rosette-forming cells gave an excellent response to KLH and also produced an active supernatant (lymphokine). Cells not forming spontaneous E-rosettes were inactive and could not produce active supernatants. Only those nonimmune cells that formed E-rosettes could respond to active supernatants. Thus, the LAI response is a specific indicator of cell-mediated immunity. T lymphocytes probably are required both at the antigen-reactive stage and at the stage of responding to the T cell-dependent lymphokine.
Cellular Immunity to Solubilized Tumor Antigens of a Methylcholanthrene-Induced Sarcoma with a Migration Inhibition Assay
Authors: Padarathsingh Martin L. , Dean Jack H. , McCoy James L. , Lewis Dale D. , Northing John W. , Natori Takashi , Law Lloyd W. 
Published: December 2022

Abstract
BALB/c mice immunized with Nonidet P-40 (NP-40) crude solubilized (CS) extracts of a syngeneic methylcholanthrene-induced BALB/c sarcoma (Meth A) were challenged with viable Meth A cells to determine the ability of the solubilized preparations to induce transplantation rejection. Animals resisting such challenge were then used in agarose microdroplet macrophage migration inhibition (MMI) and tumor cell neutralization (Winn) assays to evaluate the antigenic specificity of these CS extracts. Spleen cells from those animals that rejected Meth A after immunization with the NP-40-solubilized preparations effectively neutralized the tumorproducing capacity of Meth A tumor cells as determined in Winn assays. MMI assays were quite sensitive and detected migration inhibition of peritoneal exudate (PE) cells from immunized mice with extract concentrations as low as picogram quantities. Specificity studies demonstrated that Meth A expressed no antigenic cross-reactivity with similarly prepared extracts of an unrelated SV40-induced sarcoma (mKSA), nor with a mineral oilinduced plasmacytoma (ADJ-PC5) of BALB/c mice. Inhibition of PE cell migration was mediated by culture supernatants (presumably migration inhibition factor [MIF]) generated from a mixture of immune spleen cells and mitomycin C (MMC)-treated Meth A cells as assayed in an indirect MMI test.
Sequential Expression of Immunoglobulin on Developing Mouse B Lymphocytes: A Systematic Survey That Suggests a Model for the Generation of Immunoglobulin Isotype Diversity
Authors: Abney Erika R. , Cooper Max D. , Kearney John F. , Lawton Alexander R. , Parkhouse R. M. E. 
Published: December 2022

Abstract
Paired immunofluorescent staining with antibodies specific for the major isotypes of mouse immunoglobulin was used to study the ontogenetic expression of diversity of cell surface immunoglobulin. The first B lymphocytes to emerge, derived from cytoplasmic IgM+ precursors, express sIgM exclusively. Between birth and 3 days of age separate populations of sIgM+ B lymphocytes acquire a second isotype: sIgD, one of the subclasses of sIgG, or sIgA. At 3 days, all splenic B lymphocytes that bear sIgG or sIgA also express sIgM, but virtually none stain for sIgD. By 7 days, a substantial proportion of sIgG+ or sIgA+ lymphocytes in spleen and most of those in lymph node express both sIgM and sIgD. Anti-µ antibody treatment from birth prevented development of B lymphocytes expressing any isotype. These observations suggest that the immature sIgM+ B lymphocyte is the pivotal cell in the generation of the different sublines of B cells and that sIgD is acquired as a third isotype on B lymphocytes already committed to eventual synthesis of IgG or IgA. The frequency of lymphocytes bearing only sIgG or sIgA is higher in old than in young mice, suggesting that sIgD and sIgM may be lost after stimulation by antigens. The occurrence of a nearly identical distribution of sIg isotypes on B lymphocytes from athymic, pathogen-free mice suggests that primary expression of isotype diversity does not require T cells.
Antibodies of Restricted Heterogeneity Directed against the Cardiac Glycoside Digoxin
Authors: Zurawski Vincent R. , Novotny; Jiri , Haber Edgar , Margolies Michael N. 
Published: December 2022

Abstract
Intravenous injection of New Zealand White rabbits with type III pneumococcal polysaccharide vaccine conjugated with the cardiac glycoside digoxin resulted in the production of both antidigoxin and anti-type III pneumococcal polysaccharide antibodies. Among antisera of 12 rabbits examined during their peak antibody production periods, 1 to 20 mg (mean, 5.4 mg) of antidigoxin antibody could be recovered from 1 ml of serum. Antisera from five of these 12 rabbits contained antidigoxin antibodies of restricted heterogeneity as demonstrated by urea-polyacrylamide disc gel electrophoresis of fully reduced and alkylated antibodies. From the antisera of four of these five rabbits, electrophoretically homogeneous antibodies (1 to 5 mg/ml antiserum) could be isolated by affinity chromatography on ouabainamine-Sepharose columns. The structural homogeneity of two of these antidigoxin antibodies was confirmed by amino acid sequence analysis of purified light chains through the first hypervariable region. These data suggest that the conjugation of small molecules to bacterial polysaccharide vaccines may provide a general method for synthesis of immunogens that can regularly elicit antihapten antibodies of restricted heterogeneity.
Subpopulations of Splenic T Cells Regulating an Anti-Hapten Antibody Response
Authors: Muirhead Donna Y. , Cudkowicz Gustavo 
Published: December 2022

Abstract
In adoptive transfer experiments, two classes of peripheral T lymphocytes, carrier-primed helper (TH) and carrier-primed amplifier (TA) cells, synergized in the induction of a primary anti-hapten IgG response by virgin B cells. Purified TH and TA had separate functions and were required at different times during the antigen-driven development of the response. TH were required early, and provided an initiating signal to B cells in the presence of the specific hapten-carrier conjugate. The differentiative nature of this signal was inferred from the threshold dose-response relationship and the insensitivity of the TH-directed event to the antimitotic agent vinblastine. TA were required 4 days later and provided an amplifying signal to B cells in the presence of the same hapten-carrier conjugate. The proliferative nature of this second signal was inferred from the exponential dose-response relationship and the exquisite sensitivity of the TA-directed event to vinblastine. Virgin B cells became susceptible to the TA signal only after having received the TH signal. TH and TA did not synergize, however, in true secondary responses since haptenprimed B cells depended only on the TH signal to generate large numbers of IgG antibody-forming cells.
Genetic Control of Susceptibility of Mice to Rous Sarcoma Virus Tumorigenesis
Authors: Whitmore Alan C. , Babcock George F. , Haughton Geoffrey 
Published: December 2022

Abstract
The inheritance of suceptibility of mice to primary sarcomas induced by neonatal injection of RSV-induced chicken tumor material was studied in segregating populations derived from F1 hybrids between the resistant strain A.SW (H-28) and the susceptible strains A/WySn, B10.A (both H-2a), CBA/J (H-2k), and C57BL/10 (H-2b). In F1 hybrids between A.SW and each of the four susceptible strains, resistance is apparently dominant. In (A/WySn × A.SW) F2, (A.SW × B10.A) F2, and (A.SW × CBA/J) F2 generations tumor incidence was significantly associated with H-2 type. H-2aa and H-2kk homozygotes were as susceptible as A/WySn, B10.A, and CBA/J parental strain mice; and H-2ss homozygotes were as resistant as A.SW parental mice. H-2as and H-2ks heterozygotes were of intermediate susceptibility. No evidence was seen for association of susceptibility with three coat color genes or with sex. There was no maternal influence on inheritance of suceptibility. In a (B10.LP × A.SW) × C57BL/10 backcross generation H-2sb segregants were significantly more resistant to Rous tumorigenesis than were H-2bb segregants. No influence of genes linked to agouti or of X-linked genes was seen in this backcross generation. When mice of high and low primary tumor incidence strains were immunized with the same allogeneic Rous sarcomas, resistant strain mice developed stronger cellular anti-Rous tumor immunity (as measured by the Winn lymphocyte-tumor cell cotransfer assay) than did susceptible strain mice.
Antigen Recognition by Primed T Lymphocytes in Vitro
Authors: Greenberg Philip D. , Bluestein Harry G. 
Published: December 2022

Abstract
Antigen-induced T cell activation can be separated into early recognitive events and later proliferative events. After in vitro challenge of primed lymphocytes with antigen, enhanced transmembrane transport of α-aminoisobutyric acid (14C-AIB), a nonutilizable amino acid, can be demonstrated within 4 to 8 hr, and is at or near maximum by 8 to 16 hr of culture. The response is antigen specific and requires that the primed animal is a genetic responder to the immunizing antigen. Therefore, AIB uptake was utilized as a probe of antigen recognition and compared to tritiated thymidine incorporation, a measure of DNA synthesis. Colchicine, cytochalasin B, and Ca++ depletion have been reported to block DNA synthesis in activated lymphocytes and to interfere with macrophage-T cell interaction. We confirmed that these agents effectively abrogated antigen-induced DNA synthesis under conditions which, in contrast, had little effect on antigen-induced AIB uptake. We interpret these results to indicate at least a two-signal model for antigen-induced T cell proliferation. An initial signal is generated by the interaction of antigen with its membrane receptor. Lymphocyte activation commences but at some step before the initiation of S-phase, a second critical event, which can be blocked by colchicine, cytochalasin B, and Ca++ depletion, must occur. Since those agents block macrophage-T cell binding, the second signal may be the result of that cell-cell binding.
In Vitro Secondary MLR
Authors: Fathman C. Garrison , Watanabe Takeshi , Augustin Andrei 
Published: December 2022

Abstract
With cells obtained from long-term mixed lymphocyte culture (MLC) we have demonstrated hybrid histocompatibility determinants that are recognized as mixed lymphocyte reaction (MLR)-stimulating determinants. Hybrid determinants can also be detected (1) in an in vitro assay for effector cells that measure inhibition of immunoglobulin secretion by LPS-blasts, and (2) in DTH-like responses of in vitro-primed cells injected into “B” mice and challenged in vivo with stimulator cells.
The possible implications of these findings for the physiologic function of MLR determinants are discussed.
Human Cytotoxic Response in Vitro to Trinitrophenyl-Modified Autologous Cells
Authors: Shaw Stephen , Nelson David L. , Shearer Gene M. 
Published: December 2022

Abstract
Peripheral blood leukocytes from all normal humans tested have generated trinitrophenyl (TNP)-dependent cytotoxic activity after in vitro sensitization with TNP-modified autologous cells. Weak cytotoxic activity was generated during primary culture; total cytotoxic activity increased approximately 100-fold during secondary stimulation and another 5-fold during tertiary stimulation. The cytotoxic activity was shown to be TNP-dependent at both the sensitization and the lytic phases. Effectors lysed not only TNP-modified autologous cells but all TNP-modified human leukocyte targets tested, including those that shared no serologically defined HLA-A, -B, or -C locus determinants with the specific target. This cross-reactivity was species specific, since it was not observed when human effectors were tested on TNP-modified mouse targets. The TNP-dependent cytotoxic activity on autologous and unrelated cells was shown to be mediated by T cells without requirement for Fc-bearing cells; cytotoxic activity was recovered in subpopulations of cells positively selected by sheep erythrocyte-rosetting techniques and in subpopulations negatively selected by depletion of phagocytic cells, sIg-positive lymphocytes, and Fc-receptor positive lymphocytes. Furthermore, unlike ADCC mediated by anti-TNP antibody, the cytotoxic activity was inhibited by TNP-modified autologous cells, but not by TNP-lysine, or TNP-conjugated chicken red blood cells. We conclude that some human cytotoxic T cells raised against TNP-modified autologous cells because they express a receptor for TNP in conjunction with cell surface determinant(s) that are widely shared among humans but not shared with mice.
Corticosteroids Block Newly Induced but Not Constitutive Functions of Macrophage Cell Lines: Myeloid Colony-Stimulating Activity Production, Latex Phagocytosis, and Antibody-Dependent Lysis of RBC and Tumor Targets
Authors: Ralph Peter , Ito Masami , Broxmeyer Hal E. , Nakoinz Ilona 
Published: December 2022

Abstract
Hydrocortisone at 10-4 M added to macrophage cell lines had no effect on the following activities: J774.1 antibody-dependent phagocytosis and lysis of sheep RBC, RAW 264 antibody-dependent lysis of tumor targets, latex bead phagocytosis by PU5-1.8 cells, and constitutive production of myeloid colony-stimulating activity (CSA) by WEHI-3 cells. In contrast, 10-4 M hydrocortisone completely inhibited LPS or PPD activation of the following functions: induced production of myeloid CSA, stimulation of latex phagocytosis and stimulation of antibody-dependent lysis of tumor targets by PU5-1.8 cell line, and stimulation of antibody-dependent lysis of RBC targets by RAW 264 cell line. Lower concentrations of hydrocortisone or dexamethasone at 10-6 M inhibited the LPS induction of CSA from 55 to 90%. Growth inhibition of PU5-1.8 cells caused by 1 µg/ml LPS was also partially reversed by corticosteroids. Thus, steroids block these newly induced but not constitutive functions of these macrophage cells in culture.
Anti-Immunoglobulin Stimulation of Murine Lymphocytes
Authors: Scribner Duncan J. , Weiner Howard L. , Moorhead John W. 
Published: December 2022

Abstract
Anti-immunoglobulin (anti-Ig) antibodies can stimulate B cell proliferation in spleen cell cultures from aged (greater than 7 to 9 months) but not young (less than 5 to 7 months) mice. The response appears to be T-independent since anti-θ and complement treatment did not diminish responsiveness of B cells from aged mice. The lack of responsiveness of spleen cells from young mice is not due to suppressor T cells: 1) T cell-depleted, B cell-enriched cultures of spleen cells from young mice remained unresponsive to anti-Ig and 2) responsiveness of B cells from aged mice was not suppressed by co-culture with spleen cells, purified splenic T cells, or thymocytes from young mice.
Additional experiments in which the stimulating ability of intact anti-Ig was compared to its Fab′2 counterpart (Fab′2 anti-Ig) revealed two significant findings. First, B cells from young mice that are normally unresponsive to intact anti-Ig were found to respond quite well to Fab′2 anti-Ig. This response, measured at 72 hr of culture, was profoundly inhibited by intact anti-Ig, even when the latter was added at 48 hr. This indicates that active B cell proliferation can be inhibited by interactions of anti-Ig molecules with Fc receptors. Second, B cells from aged mice were found to respond significantly better to Fab′2 anti-Ig than to the intact molecule. However, addition of intact anti-Ig to these Fab′2-stimulated cultures resulted in relatively poor inhibition of the response. These results indicate that the ability of mouse B cells to respond to anti-Ig is related to the efficiency of Fc receptors in mediating inhibitory signals and further suggest that the aging process in the mouse is accompanied by a decline in B cell regulation intrinsic to the B cell itself.
Genetic Control of T Lymphocyte Responses by in Vitro Sensitization with Macrophage-Bound Antigens
Authors: Thomas David W. 
Published: December 2022

Abstract
The genetic factors involved in the guinea pig response to the copolymer of l-glutamic acid and l-lysine (GL), responsiveness which is linked to the I-region of the strain 2 major histocompatibility complex, have been further analyzed by in vitro priming of nonimmune T lymphocytes with GL-pulsed syngeneic or semi-syngeneic macrophages. Responder strain 2 T cells could be specifically sensitized by culture for a week with GL-pulsed strain 2 macrophages and produced an increased DNA synthetic response upon restimulation with GL in the presence of fresh strain 2 macrophages. In contrast, nonresponder strain 13 T cells failed to become sensitized to GL-pulsed strain 13 macrophages, but could be specifically primed by culture with ovalbumin (OVA)-pulsed strain 13 macrophages. In addition, (2 × 13)F1 T cells primed by culture with GL-pulsed strain 2 or (2 × 13)F1 macrophages could be restimulated with GL only in the presence of strain 2, but not of strain 13, macrophages. F1 T cells failed to demonstrate sensitization with GL-pulsed nonresponder strain 13 macrophages, but showed OVA-specific priming with OVA-pulsed strain 13 macrophages. These results indicate that genetic control of the response to GL by in vitro sensitization with GL-pulsed macrophages is similar to that previously observed by immunization of guinea pigs with soluble GL and support the proposal that unresponsiveness to GL represents a defect in cellular recognition.
Inhibition of Human Urinary Kallikrein (Urokallikrein) by Anti-Enzyme Fab
Authors: Ole-Moiyoi Onesmo , Spragg Jocelyn , Austen K. Frank 
Published: December 2022

Abstract
Monospecific rabbit IgG and Fab antibodies against human urokallikrein inhibit the proteolytic and esterolytic functions of the enzyme in a substrate dose-dependent fashion, indicating an antibody specificity for antigenic determinants at the active site of the enzyme. The specific anti-urokallikrein Fab fragments exhibited charge heterogeneity on isoelectric focusing but were oligoclonal in comparison with the distribution of the entire Fab pool. The inhibition of the kinin-generating activity of urokallikrein by the specific Fab fragments was complete at 30 sec, the earliest time interval measured. The average inhibition constant for the specific monovalent Fab fragments is the same as for the specific IgG, namely, 2.2 × 10-8 M, a finding compatible with the observations of others employing haptenic determinants. Since the molar concentrations required for comparable inhibition by anti-urokallikrein Fab were greater than the molar concentrations of anti-urokallikrein IgG, the inhibition of enzyme function by anti-urokallikrein IgG reflects both active site neutralization and additional nonspecific effects including precipitation. Analysis of the inhibition of urokallikrein kiningenerating activity by anti-urokallikrein Fab by the method of Dixon indicated the mechanism to be competitive. The additional finding that anti-urokallikrein Fab gave a dose-related inhibition of the action of urokallikrein on incremental concentrations of the synthetic substrate, α-N-p-tosyl-l-arginine methyl ester, indicated action at the active site. Analysis of these data by Dixon plots revealed competitive inhibition at the lower concentrations of Fab with an average inhibitory constant of 2.5 × 10-7 M and mixed inhibition at higher concentrations, thereby suggesting the presence of some specificities for antigenic determinants other than those at the active site. These studies demonstrate that anti-urokallikrein IgG yields a population of anti-urokallikrein Fab directed so as to neutralize proteolytic and esterolytic functions of the enzyme by a competitive mechanism.
Studies on the Immune Response to Fixed Antigens
Authors: Leshem B. , Naor D. 
Published: December 2022

Abstract
Heavy trinitrophenylated sheep red cells (TNP 128SRC) and glutaraldehyde-treated SRC (G-SRC) could not induce cellular cytotoxicity against 51Cr-SRC. In contrast, the native antigen SRC could stimulate a cytolytic response against the radiolabeled homologous target cell. However, fixed SRC could stimulate a priming function that accelerated and augmented the secondary cytotoxic response to SRC. Such fixed antigens could stimulate a delayed-type hypersensitivity (DTHS) response also. Thus, the immunologic memory to the chemically modified antigen, as well as the DTHS response, are completely dissociated from the primary cytotoxic responses.
The primary and the secondary cytotoxic responses that were developed in the spleens of the injected mice were mediated by antibody-dependent cellular cytotoxicity (ADCC), since the active supernatant that was released from the spleen cells could lyse the target cells in the presence of normal splenocytes. The active supernatant was identified as antibody. We suggest that B effector cells cytolyzed the antibody-coated target cells. Normal cells from nude mice could mediate the cytolytic process as efficiently as spleen cells from other strains of mouse. The results are discussed in terms of selective stimulation of T cell subpopulations.