bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a tumor-specific immunotherapy model utilizing TNP-reactive helper T cell activity and its application to the autochthonous tumor system.
Authors: Fujiwara H , Aoki H , Yoshioka T , Tomita S , Ikegami R , Hamaoka T 
Published: December 2022

Abstract
Preinduction of potent hapten-reactive helper T cell activity and subsequent immunization with hapten-coupled syngeneic tumor cells result in enhanced induction of tumor-specific immunity through T-T cell collaboration between anti-hapten helper T cells and tumor-specific effector T cells. On the basis of this augmenting mechanism, a tumor-specific immunotherapy protocol was established in which a growing tumor regresses by utilizing a potent trinitrophenyl (TNP)-helper T cell activity. C3H/He mice were allowed to generate the amplified (more potent) TNP-helper T cell activity by skin painting with trinitrochlorobenzene (TNCB) after pretreatment with cyclophosphamide. Five weeks later, the mice were inoculated intradermally with syngeneic transplantable X5563 tumor cells. When TNCB was injected into X5563 tumor mass, an appreciable number of growing tumors, in the only group of C3H/He mice in which the amplified TNP-helper T cell activity had been generated were observed to regress (regressor mice). These regressor mice were shown to have acquired tumor-specific T cell-mediated immunity. Such immunity was more potent than that acquired in mice whose tumor was simply removed by surgical resection. These results indicate that in situ TNP haptenation of the tumor cells in TNP-primed mice can induce the enhanced tumor-specific immunity leading to the regression of a growing tumor. Most importantly, the present study further investigates the applicability of this TNP immunotherapy protocol to an autochthonous tumor system. The results demonstrate that an appreciable percent of growing methylcholanthrene-induced autochthonous tumors regressed by the above TNP immunotherapy protocol. Thus, the present model provides an effective maneuver for tumor-specific immunotherapy in syngeneic transplantable as well as autochthonous tumor systems.
Lyt-2- T cell-independent functions of Lyt-2+ cells stimulated with antigen or concanavalin A.
Authors: von Boehmer H , Kisielow P , Leiserson W , Haas W 
Published: December 2022

Abstract
Approximately 30% of cytolytic Lyt-2+ clones from primed mice are able to proliferate autonomously, i.e., independent of IL 2 derived from Lyt-2- cells after antigenic stimulation. H-2K- or -D-restricted induction of Lyt-2+ cells to autonomous proliferation requires Ia+ stimulator cells. A strict correlation was observed between the ability of Lyt-2+ clones to proliferative autonomously and to induce DH. Eventually, the growth of all Lyt-2+ cytolytic clones becomes dependent on exogenous IL 2, and their ability to induce DH is lost. Small Lyt-2+ cells can also be induced in primary cultures by antigen or concanavalin A to proliferate in the absence of exogenous IL 2. The frequency of autonomously proliferating small Lyt-2+ cells is the same as that of small Lyt-2+ cells proliferating in the presence of exogenous IL 2. IL 2 derived from Lyt-2- cells can augment proliferation of Lyt-2+ cells, but is not obligatory.
In vivo administration of anti-I-A antibody induces the internalization of B cell surface I-A and I-E without affecting the expression of surface immunoglobulin.
Authors: Fultz M , Finkelman F D , Mond J J 
Published: December 2022

Abstract
Injection of a hybridoma anti-Ia antibody into adult mice results in a dramatic reduction in the expression of B cell sIa without affecting the expression of sIgD or sIgM. This anti-Ia-mediated modulation of B cell sIa occurs within 3 hr and attains it maximum effect within 18 hr after injection of antibody. There is a rapid reexpression of B cell Ia when such sIa- B cells are cultured in vitro. Culture of B cells in vitro with anti-Ia antibody has no discernible effect on the expression of B cell sIa, nor does it prevent the reexpression of sIa on sIa- B cells obtained from anti-Ia-injected mice. Injection of anti-I-A antibody suppresses the expression of both I-A and of I-E, and similarly, injection of anti-I-E suppresses the expression of B cell I-E and I-A antigens. When fluorescein-labeled monoclonal anti-I-A antibody is injected into mice, a significant fraction of B cell sIa can be demonstrated to be internalized by the B cell. The potential immunologic significance of this phenomena of anti-Ia-mediated modulation of B cell sIa is discussed.
Plasmodium berghei sporozoites are mitogenic for murine T cells, induce interferon, and activate natural killer cells.
Authors: Ojo-Amaize E A , Vilcek J , Cochrane A H , Nussenzweig R S 
Published: December 2022

Abstract
Enhanced natural killer (NK) activity was detected in the spleens of mice as early as 24 hr after single i.v. inoculation with gamma-irradiated Plasmodium berghei sporozoites. The activity peaked at 48 hr post-injection, and declined below baseline level by day 8. Reinoculation of mice with irradiated sporozoites produced an increased NK activity significantly smaller than the original activity. Spleen cells sensitized in vivo as well as nonsensitized spleen cells stimulated in vitro with sporozoites produced high levels of interferon (IFN) and displayed enhanced NK activity. Characterization of the IFN through the use of specific antibodies revealed that it was mainly IFN-gamma. The cellular basis for IFN-gamma induction was linked to the mitogenicity of P. berghei sporozoites for T cells. The possibility exists that IFN-gamma may have a regulatory effect on antibody production against P. berghei sporozoites.
Dissociation of severe lupus-like disease from polyclonal B cell activation and IL 2 deficiency in C3H-lpr/lpr mice.
Authors: Davidson W F , Roths J B , Holmes K L , Rudikoff E , Morse H C 
Published: December 2022

Abstract
The lymphoproliferation characteristic of all strains of mice homozygous for the gene lpr results from the expansion of an unusual subset of cells that express reduced levels of Ly-1 and Thy-1 antigens and high levels of Ly-5(B220), an antigen that is normally only detected on cells of the B lineage. In the present study, C3H-lpr mice were studied to determine when this population of cells first appears in lymph node (LN) and spleen and whether its appearance relates to the development of B cell activation and deficiencies in interleukin 2 (IL 2) production. The results showed that Ly-5(B220)+, sIg- cells were first detected in LN at 4 wk of age; thereafter their numbers increased exponentially until at 16 wk of age they represented more than 80% of LN cells. Two subpopulations of Ly-5(B220)+, sIg- cells were present in LN; one Ly-1+, Thy-1+ and the other Ly-1+, Thy-1-. Ly-5(B220)+, sIg- cells were not detected in C3H-lpr spleen until 6 to 10 wks after their appearance in LN, and their proportions never reached those in LN. Polyclonal B cell activation in C3H-lpr spleens was not observed until Ly-5(B220)+, sIg- cells were present, suggesting that this population may play a role in B cell stimulation. IL 2 production by C3H-lpr spleen and LN cells was normal up to 6 wk of age and was significantly impaired thereafter, with LN being more severely affected than spleen. The IL 2 defect could be significantly repaired by the addition of PMA to the cultures. Although defective IL 2 production coincided with the appearance of Ly-5(B220)+, sIg- cells in LN, it preceded the appearance of these cells in spleen. In spite of the impaired ability to produce IL 2 in vitro, CTL responses to alloantigens were normal. Although C3H-lpr mice share many of the lymphoid abnormalities observed in MRL-lpr mice, they do not develop severe, early-onset SLE-like disease characteristic of the latter strain. This suggests that factors other than defective IL 2 production and polyclonal B cell activation are required for the development of fulminant autoimmune disease.
Generation of human C3a, C4a, and C5a anaphylatoxins by protein A of Staphylococcus aureus and immobilized protein A reagents used in serotherapy of cancer.
Authors: Langone J J , Das C , Bennett D , Terman D S 
Published: December 2022

Abstract
Protein A (SpA) alone or immobilized on bacteria (e.g., Cowan strain I), collodion charcoal, or on Sepharose have been used in serotherapy of cancer in humans and experimental animals. Because SpA forms complexes with IgG that can activate complement, and the physiologic response during treatment often involves hypocomplementemia and reactions that are similar to those induced by anaphylatoxins, we used sensitive and specific radioimmunoassays to test the ability of SpA reagents to generate C3a, C4a, and C5a from human serum. The yield of anaphylatoxins depended on the dose of SpA, with the maximum generation of C3a (47 to 55 micrograms/ml) and C5a (1.4 to 1.9 micrograms/ml) being produced with levels of SpA that were maximally precipitated from serum. Maximum C4a levels (up to 15 micrograms/ml) were obtained at concentrations of SpA equal to or greater than the dose required to give optimal precipitation. The maximum concentrations of anaphylatoxins correspond to essentially quantitative conversions of C3 to C3a, C4 to C4a, and 40% of C5 to C5a after correction for levels found in serum incubated in pyrogen-free saline. Preformed insoluble complexes prepared from either serum or monomeric IgG also were capable of generating anaphylatoxins in fresh whole serum up to levels approximately equal to those observed in serum treated directly with an optimal amount of SpA. The preformed complexes from serum or IgG generated similar high concentrations of anaphylatoxins when carried through four sequential incubations with fresh serum, and complexes that contained approximately 1 microgram SpA were still active. Preincubating the insoluble complexes with chicken anti-SpA serum did not alter their activity. Incubation of serum with collodion charcoal coated with SpA, in a system that models the perfusion technique used to treat cancer, produced complexes that generated significant levels of C3a compared with levels found in serum passaged over albumin charcoal or in untreated serum. The C3a levels in serum from the albumin collodion charcoal were not significantly different from those found in untreated serum. Similar amounts of C3a, C4a, or C5a were observed in serum incubated with differing numbers of bacteria representing a strain of S. aureus rich in cell bound SpA (Cowan strain I) or a strain (Wood 46) deficient in SpA. This suggests that in intact bacteria, cell wall factors other than SpA (e.g., peptidoglycan) are predominantly responsible for generating anaphylatoxins.(ABSTRACT TRUNCATED AT 400 WORDS)
Quantitative analysis of Fc gamma receptors on murine spleen cell populations by using dual parameter flow cytometry.
Authors: Titus J A , Finkelman F D , Stephany D A , Jones J F , Segal D M 
Published: December 2022

Abstract
The expression of Fc gamma R on subsets of mouse spleen cells was examined by dual parameter flow microfluorometry. B cells were detected by labeling them with antibodies against sIgM, sIgD, sIgG, or I-A; essentially all B cells expressed Fc gamma R. The number of Fc gamma R per cell on the sIgD+, sIgM+, and I-A+ cells averaged 2 X 10(4) receptors, and no correlation between the levels of expression of Fc gamma R and the B cell markers was evident. The sIgG+ B cells, however, expressed more Fc gamma R (8 X 10(4) receptors/cell) than sIgM+ and sIgD+ B cells. Fc gamma R on splenic macrophages were examined by double labeling spleen cells for Fc gamma R and Mac-1. The Mac-1+ cells (2 to 16% of the spleen cells) were 100% Fc gamma R+ and expressed threefold to fivefold higher numbers of Fc gamma R per cell than the sIgM+ or sIgD+ B cells. The Fc gamma R on T cells were studied on cells double labeled for Fc gamma R and Thy-1, Lyt-1, or Lyt-2. An average of 20% of the T cells expressed Fc gamma R and at least two subsets of Fc gamma R+ T cells were evident: Lyt-2- cells, most of which expressed intermediate (2 X 10(4) Fc gamma R/cell) levels of Fc gamma R, and Lyt-2+ cells, which expressed mainly high (8 X 10(4) Fc gamma R/cell) amounts of Fc gamma R. The levels of expression of Fc gamma R and sIgM increased dramatically in response to infection and were elevated in mice with genetic defects. We conclude that the level of Fc gamma R expression is a characteristic property of subsets of spleen cells from normal and infected mice.
Anti-immunoglobulin antibodies. V. Age-dependent variation of clones stimulated by polysaccharide TI-2 antigens in 129 and MRL mice spontaneously producing anti-gamma-globulin antibodies.
Authors: Manheimer A J , Victor-Kobrin C , Stein K E , Bona C A 
Published: December 2022

Abstract
The nature of the immune response to two conventional polysaccharide thymus-independent (TI) antigens was investigated in two RF-producing mouse strains, the 129/Sv and MRL/1 pr, as well as in their normal congenic counterparts, 129/J and MRL +/+ animals. An age-dependent variation of clones specific for the TI-2 antigens bacterial levan (BL) and alpha 1, 3 dextran B1355 (Dex) was observed in 129/J mice. Surprisingly, the anti-BL and anti-Dex responses observed for young (1-mo-old) 129/Sv mice far exceeded those of their age-matched controls indicating an accelerated ontogenic development of the immune response to TI-2 antigens. A poor response was observed for both MRL +/+ and MRL/1 pr mice after immunization with BL. More importantly, MRL mice, unlike other H-2k, Igh.Ca strains, were unresponsive to Dex in CFA or saline. MRL mice, however, could respond to the T-dependent form of this antigen, Dex-KLH, suggesting that these mice lack the subset of B cells required to respond to TI-2 antigens. Finally, the most striking observation was the occurrence of isotype-specific RF subsequent to immunization with these antigens in animals prone to develop RF, as well as in aged animals that do not spontaneously produce RF.
Expression of IgE receptors and histamine in cloned natural killer cell lines.
Authors: Rosenthal K L , Ishizaka T , Befus D , Dennert G , Hengartner H , Bienenstock J 
Published: December 2022

Abstract
Natural killer (NK) activity is mediated by large granulated lymphocytes (LGL). Recently, the relationship of NK cells to mast cells and basophils has been suggested. We therefore examined three distinct interleukin 2-dependent cloned cell lines capable of mediating NK lysis. Virtually all the cells of each line contained membrane-bound granules. Interestingly, ultrastructural studies demonstrated that the granules in each cell line were morphologically distinct and thus heterogeneous. All three cloned, granulated NK cell lines were found to variably express low numbers (less than or equal to 1.3 X 10(4)) of low affinity plasma membrane IgE receptors (Fc epsilon R). In contrast to mast cells and basophils, however, none were found to express high numbers of high affinity Fc epsilon R. In addition, none of the three NK cell lines were found to contain histaminase-sensitive histamine. Our results suggest that NK cells are not related to mast cells or basophils.
Monoclonal antibodies reactive with swine lymphocytes. I. Antibodies to membrane structures that define the cytolytic T lymphocyte subset in the swine.
Authors: Jonjić S , Koszinowski U H 
Published: December 2022

Abstract
A panel of monoclonal antibodies (mAb) with specificity for swine leukocytes was prepared by somatic cell hybridization with the use of spleen cells from mice immunized with swine thymocytes. The reactivity of two mAb (295/33 and 122/28), which both immunoprecipitated from the surface of swine leukocytes an antigen termed S-L2 with an apparent m.w. of 33 to 35 kilodaltons under reducing and 65 to 70 kilodaltons under nonreducing conditions, was investigated in detail. These mAb were reactive in indirect immunofluorescence with 50 to 60% of thymocytes, 35% of peripheral blood lymphocytes, and 55% of E rosette-positive cells; they were nonreactive with bone marrow cells, Ig+ B cells, nonrosetting lymphocytes, granulocytes, and monocytes. In functional studies, the elimination of S-L2+ cells partially reduced the proliferative response to concanavalin A and pokeweed mitogen but not to Staphylococcus aureus and lipopolysaccharide. The S-L2- subset proliferated well to alloantigens. Both cytolytic T effector cells and precursor cells carried the antigen S-L2 and could be depleted from heterogeneous cell populations by both antibodies in the presence of complement. These data suggest that the mAb 295/33 and 122/28 recognize a specific polypeptide present on the surface of swine cytolytic T cells. These antibodies will be useful in studies on the swine immune system.
Direct effects of a monoclonal B cell differentiation factor and of purified interleukin 1 on B cell differentiation.
Authors: Falkoff R J , Butler J L , Dinarello C A , Fauci A S 
Published: December 2022

Abstract
We have previously described the presence of factors in mixed lymphocyte culture supernatants that induce activated but not resting human B cells to secrete Ig. In the present study, we describe the effects of a B cell differentiation factor in the supernatant (SN) of a T-T hybridoma (clone 7D5). We find that it induces Ig secretion by human B cells in the absence of T cells or monocytes. It acts only on activated B cells, because small (resting) B cells isolated by centrifugal counterflow elutriation do not respond to it, whereas the same cells do develop into Ig-secreting cells if activated in culture with Staphylococcus aureus Cowan I before exposure to SN 7D5. By using class-specific reagents in enzyme-linked immunosorbent assays, we found SN 7D5 to result in the secretion of significant amounts of IgM, IgG, and IgA. We also studied the effects of highly purified interleukin 1 on this differentiation process. Interleukin 1 by itself failed to induce Ig secretion by activated B cells, and its presence was not required for the induction of Ig secretion by SN 7D5. However, interleukin 1 consistently synergized with SN 7D5 in inducing Ig secretion by purified B cells.
Biologic functions of the OKT1 T cell surface antigen. I. The T1 molecule is involved in helper function.
Authors: Thomas Y , Glickman E , DeMartino J , Wang J , Goldstein G , Chess L 
Published: December 2022

Abstract
The OKT1 (Leu-1) monoclonal antibody reacts with a 69 KD glycoprotein that is present on only a fraction of functionally mature thymocytes but is maintained on most peripheral T cells. In the study presented, we examined the role of this surface molecule in T cell function. We found that addition of the OKT1 antibody to B cells and autologous T4+ cells markedly enhances B cell differentiation. This enhancement was apparent when nonirradiated or irradiated T4+ cells but not T8+ cells were used. Moreover, the OKT1 antibody as well as the OKT1 F(ab')2 fragment enhanced B cell differentiation in a dose-dependent fashion. It is important to note that perturbation of the T1 molecule with OKT1 in the presence of autologous E- cells causes the rapid release of molecules that trigger B cells to proliferate and differentiate into Ig-secreting cells. These data when considered together suggest that OKT1 reacts with a T cell membrane determinant or a complex that is intimately involved in the execution of helper function on OKT4+ cells.
Autoimmune mice develop antibodies to thymic hormone: production of anti-thymulin monoclonal autoantibodies from diabetic (db/db) and B/W mice.
Authors: Dardenne M , Savino W , Bach J F 
Published: December 2022

Abstract
Monoclonal autoantibodies specific for the thymic hormone thymulin (FTS-Zn) were obtained by cell fusion with the use of spleen cells from nonimmunized autoimmune B/W or diabetic (db/db) mice and myeloma cells. Culture supernatants were screened for their ability to inhibit in vitro and in vivo the biologic activity of synthetic and natural hormone and to bind specifically to thymic epithelial cells in indirect immunofluorescence. This binding was completely abolished by preincubation of the antibodies with the synthetic hormone. These monoclonal autoantibodies were shown by double labeling experiments to bind the same thymic epithelial cells as the antithymulin monoclonal antibodies prepared by immunization with thymic epithelial cells. These autoantibodies directed against the low m.w. thymic hormone thymulin do not explain the low thymulin serum level found in those mice because there is a concomitant decrease in the number of thymulin-containing cells in the thymus, but they could play a role in the maintenance of T lymphocyte defects observed in these mice.
Effects of natural and recombinant IL 2 on regulation of IFN gamma production and natural killer activity: lack of involvement of the Tac antigen for these immunoregulatory effects.
Authors: Ortaldo J R , Mason A T , Gerard J P , Henderson L E , Farrar W , Hopkins R F , Herberman R B , Rabin H 
Published: December 2022

Abstract
Highly enriched populations of human large granular lymphocytes (LGL), natural killer (NK) cells, and T cells were obtained from low and high density fractions, respectively, of discontinuous Percoll gradients. The NK cells were composed of 75 to 90% LGL, with the majority of the contaminating cells being monocytes. The T cells were greater than 95% OKT3+. The proliferative and cytotoxic progenitors in both fractions were examined by using a limiting dilution assay with interleukin 2 (IL 2) from four sources: 1) crude supernatant of a gibbon lymphoma (MLA-144), 2) purified (150,000-fold) MLA-144 IL 2, 3) partially purified human IL 2, and 4) purified recombinant human IL 2. The proliferative capacity was measured at day 7 by [3H]thymidine incorporation, whereas the progenitors of cells with NK-like activity were evaluated by assessing cytotoxic activity against K562 cells at day 8 in a 4-hr 51Cr-release assay. The frequency of proliferative progenitors among T cells was approximately 1/5 and was approximately 1/60 with LGL. Titration of the highly purified IL 2 preparation demonstrated that LGL proliferated with as little as 2 U of IL 2. The frequency of detectable cytotoxic progenitors in the LGL population, however, fell sharply when less than 40 U of IL 2 were employed. The T cells failed to demonstrate cytotoxic activity against the NK-susceptible target cells at any concentration of IL 2 tested. The IL 2 preparations also were examined for their ability to directly and rapidly enhance the cytotoxic activity of highly purified NK cells. All four preparations of IL 2 enhanced the cytotoxic activity of LGL without any detectable accessory requirement after incubation for as little as 6 hr, even though the MLA-144 IL 2 preparations were devoid of detectable interferons (IFN). These data indicate that IL 2 has dual effects on NK cells, regulating their activity was well as promoting their proliferation. Collectively, these results demonstrate that highly purified IL 2, devoid of other detectable lymphokines, is capable of supporting the growth of human NK cells and augmenting their in vitro activity. In parallel experiments, these same IL 2 preparations were quite active in causing the proliferation of T lymphocytes, clearly demonstrating a role of IL 2 in promoting the proliferation of NK cells as well as T cells. The mechanism of IL 2 boosting appears to be a direct interaction with LGL, resulting in the production of IFN gamma.(ABSTRACT TRUNCATED AT 400 WORDS)