bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alloantigen-induced cytotoxicity against syngeneic tumor cells: analysis at the clonal level.
Authors: Sensi M , Orosz C G , Bach F H 
Published: December 2022

Abstract
It has been shown that peritoneal exudate cells (PEC) from BALB/c mice immunized with minor histocompatibility antigens presented by DBA/2 or B10.D2 spleen cells are capable of lysing syngeneic YC8 tumor cells in a 4-hr 51Cr-release assay. In this study, we employed limiting dilution analysis to determine the frequency of CTL precursors (CTL-P) reactive against both the specific DBA/2 (or P815) target and the syngeneic tumor YC8. The mean frequency of anti-DBA/2 CTL-P in PEC from BALB/c mice immunized with DBA/2 was 1/302. Between one-third and one-fifth of limiting dilution microcultures that exhibited lytic activity against DBA/2 lymphoblasts (or P815) were also able to lyse YC8. No lysis of YC8 was observed in the absence of a parallel lysis on DBA/2 lymphoblasts or P815 target cells. T cell clones, derived by micromanipulation from microcultures selected for cytotoxic activity against YC8 and/or P815, maintained either the specific anti-allogeneic or the doubly reactive ( antiallogeneic plus anti-syngeneic tumor) phenotype. Fourteen clones (six specific and eight doubly reactive) were tested for cytotoxic activity on a panel of target cells with different haplotypes. All showed H-2-restricted specificity for minor histocompatibility antigens shared by DBA/2 and B10.D2. The restriction element for some of the clones mapped in the K region of the H-2 complex, whereas for other clones the restriction element mapped in the D region; both K- and D-restricted clones were able to lyse YC8. When the clones that exhibited lysis on YC8 were tested on two other BALB/c tumor targets, LSTRA, a Moloney virus induced lymphoma, and RL male-1, a radiation induced lymphoma, two of seven were found to lyse all three syngeneic tumor targets equally well, but not syngeneic BALB/c blasts. These clones were functionally categorized as conventional CTL because they were unable to proliferate when cultured with antigen in the absence of exogenous lymphokines, and were unable to produce lymphokine with IL 2 activity when stimulated by the appropriate splenocytes. When tested in vivo in a Winn assay, a strong anti-tumor activity against YC8 was exerted by the anti-DBA/2 clones DY4 -3 and DY16 -3. These clones lysed both YC8 and the immunizing target cells in vitro. No in vivo effect in neutralizing YC8 tumor growth was observed with clone D2-1, a clone that lysed DBA/2 targets but not YC8 in vitro.
Specific inhibition of in vitro lymphocyte transformation by an anti-pan T cell (gp67) ricin A chain immunotoxin.
Authors: Kernan N A , Knowles R W , Burns M J , Broxmeyer H E , Lu L , Lee H M , Kawahata R T , Scannon P J , Dupont B 
Published: December 2022

Abstract
The toxin A chain of ricin has been conjugated by a disulfide bond to a murine monoclonal antibody that recognizes the gp67kD antigen present on 95% of peripheral T lymphocytes. The immunotoxin retains both functions of its component parts: it binds to human peripheral blood lymphocytes, and it inhibits protein synthesis in a cellfree reticulocyte system. The immunotoxin has been evaluated for its ability to inhibit in vitro T lymphocyte transformation. In the presence of 20 mM NH4Cl, the immunotoxin decreases lymphocyte proliferation in response to phytohemagglutinin to less than 8% of untreated controls. The proliferative response in mixed lymphocyte culture and the development of allocytotoxic T cells is also dramatically inhibited by this immunotoxin. Monoclonal antibody alone does not inhibit these responses. Specificity of the immunotoxin has been established: the effect of the immunotoxin can be blocked by unconjugated monoclonal antibody, but not by a control monoclonal antibody that recognizes another T lymphocyte differentiation antigen or by a control monoclonal antibody that does not recognize human peripheral blood leukocytes. Treatment of human bone marrow cells with the immunotoxin preserves hematopoietic progenitor cells, as measured by granulocyte-macrophage, erythroid, and multipotential hematopoietic progenitor cell assays. These results indicate that an anti-pan T lymphocyte-ricin A chain immunotoxin is an effective agent against immunocompetent T lymphocytes in vitro, and may be an effective agent for use in clinical bone marrow transplantation.
Glucocorticosteroids stimulate polyclonal immunoglobulin production by cord blood mononuclear cells.
Authors: Orson F M , De Seau V , Pike S , Blaese M 
Published: December 2022

Abstract
Glucocorticosteroids (GCS) are in vitro polyclonal activators of immunoglobulin (Ig) production for human mononuclear cells (MC) from virtually all adult donors. However, GCS treatment of cord blood MC resulted in Ig production in only 12/41 samples. This GCS effect is T cell and monocyte dependent and is mediated in part by a soluble T cell replacing factor. The inconsistent response of cord MC could be due to either cellular or soluble factor differences from adults. In 11/12 samples tested, irradiated cord T cells did help adult B cells, but less than did irradiated allogeneic adult T cells. T cell suppression in cord samples is unlikely inasmuch as higher cord T cell numbers and proportions increased the number of responding cord samples. Cord monocytes function adequately, because monocytes supported GCS responses when cord non-T cells had sufficient T cell help. The T cell replacing factor was found in supernatants of unstimulated cord as well as in adult MC cultures, but was less than 50% as potent. Cord B cells did not develop GCS-induced Ig production with such supernatants, suggesting that cord B cells may require a higher concentration or more prolonged exposure to T cell help. With a 2:1 ratio of irradiated adult T cells to cord non-T cells, only 25% of cord samples responded to GCS (compared to greater than 95% of adult samples), but with a ratio of 4:1, 75% responded. IgM was the predominant isotype secreted by GCS-stimulated cord cells, but 6/14 samples also produced IgG and 8/14 produced IgA. Thus, the functional immaturity of both cord T and B cells exists for GCS-induced Ig production, but with appropriate conditions GCS can activate most samples of cord B cells to synthesize Ig.
Induction of suppressor T cells by interleukin 2.
Authors: Ting C C , Yang S S , Hargrove M E 
Published: December 2022

Abstract
The optimal concentration of interleukin 2 (IL 2) for maintaining the in vitro growth of T cells was quite different from that required for the induction of cytotoxic T lymphocytes (CTL) in nu/nu spleen cells. Higher concentrations of IL 2-containing preparations (10 to 30% v/v or 5 to 15 U/ml) were needed to promote the T cell growth, whereas lower concentrations (1 to 3% v/v or 0.5 to 1.5 U/ml) were needed to generate alloreactive CTL. It was further shown that the addition of high concentrations of IL 2 (10 to 30%) suppressed the generation of alloreactive CTL in conventional MLC. High concentrations of IL 2 induced the generation of antigen-nonspecific suppressor T cells in normal spleen cell cultures and augmented the generation of antigen-specific suppressor T cells in MLC. These suppressor cells suppressed the generation of CTL in fresh MLC and in polyclonal CTL cultures. These suppressor T cells could be induced by rat (spleen)-produced, murine (EL-4 cells) produced IL 2 preparations, and a purified human recombinant IL 2 (HR-IL2). The ability to induce suppressor cells correlated with the activity of IL 2 present in these preparations and was independent of their ability to induce cytotoxic effectors. These findings indicate that IL 2 may play a dual role in the regulation of CTL responses. We suggest that during antigen sensitization, the initial endogenous production of lower levels of IL 2 provided the second signal for the differentiation and proliferation of CTL. When higher levels of IL 2 were produced later, the suppressor T cell precursors were activated and differentiated into suppressor effectors to regulate the CTL response.
Noncovalent association of heavy and light chains in Rana catesbeiana immunoglobulins.
Authors: Mikoryak C A , Steiner L A 
Published: December 2022

Abstract
The unreduced immunoglobulins (Ig) in the bullfrog, Rana catesbeiana, dissociate into two components when subjected to electrophoresis or molecular sieving in dissociating solvents. One of these components is monomeric light chain and the other is a disulfide-bonded complex of heavy chains. This unusual behavior has been observed with all classes of bullfrog Ig that have been isolated and characterized previously: a high m.w. Ig that resembles mammalian IgM and two antigenically distinct varieties of low m.w. Ig. Light chains, isolated from the high m.w. Ig by gel filtration in 8 M urea, 1 M acidic acid, were found to contain, on average, 5.7 residues of half-cystine. None of these residues were in the free sulfhydryl form nor were they blocked by half-cystine. Moreover, none was alkylated after mild reduction of the high m.w. Ig. These findings indicate that none of the light chain half-cystine residues participate in an interchain disulfide bridge, and that most of the light chains contain three intrachain bridges. This unusual pattern of disulfide bonding appears to be responsible for the noncovalent association of heavy and light chains in this species.
Influence of the immunoglobulin heavy chain locus on expression of the VK1GAC light chain.
Authors: Fulton R J , Davie J M 
Published: December 2022

Abstract
The VK1GAC light chain represents the dominant V kappa structure employed in the antibody response of A/J mice to streptococcal group A carbohydrate ( GAC ). Two anti-idiotypic antisera, anti- Id5 and anti- Id20 , with specificity for the VK1GAC light chain were used to examine anti- GAC antibody responses in a series of inbred mouse strains that differ at the heavy chain constant region ( IgCH ) allotype locus. Both idiotypes were expressed in normal and immune sera from mice of most IgCH allotypes, except IgCHb (C57BL/6J) and IgCHf (CE/J). C57BL/6J mice expressed Id5 , but not Id20 , whereas CE/J mice did not express either idiotype. Testing of recombinant inbred strains between BALB/c and C57BL/6 indicated that the pattern of idiotype expression did not correlate with IgCH allotype. The C X B recombinants expressed all three idiotype patterns that were observed in the panel of inbred strains. Testing of allotype congenic mice between BALB/c and C57BL/6 showed that CB.20 and BC.8 mice were Id20 -, whereas BAB-14 mice were Id20 +, indicating that both VH and background (V kappa or regulatory) loci must be derived from BALB/c to obtain Id20 expression. The difference in the frequency of idiotype expression observed between BALB/c and BAB-14 mice indicates that the IgCH locus may exert a quantitative influence on the expression of this light chain. To examine the Id20 -, Id5 + antibodies of C57BL/6 mice, anti- GAC hybridomas were prepared. Of 16 C57BL/6-derived anti- GAC monoclonal antibodies, six were reactive with anti- Id5 and not with anti- Id20 . Isoelectric focusing of the purified kappa light chains from three of these antibodies revealed two distinct spectrotypes that co-migrated with the two known VK1GAC spectrotypes observed with A/J anti- GAC light chains. Idiotypic analysis of in vitro recombinants between the heavy and light chains of A/J and C57BL/6 monoclonal antibodies demonstrated that the C57BL/6 light chains were idiotypically similar to A/J light chains when they were free in solution or paired with A/J heavy chains. These results demonstrate that C57BL/6 mice can express a light chain that is very similar, if not identical, to the VK1GAC light chain, although the light chain is expressed in lower frequency and is paired with a distinct VH structure, which can mask expression of one of the VK1GAC idiotypes. These effects on V kappa expression map to at least three genetic loci: VH, CH, and an unlinked locus.
Synergism between lymphokines and muramyl dipeptide encapsulated in liposomes: in situ activation of macrophages and therapy of spontaneous cancer metastases.
Authors: Fidler I J , Schroit A J 
Published: December 2022

Abstract
Murine alveolar macrophages (AM) can be rendered tumoricidal after the i.v. injection of multilamellar vesicles (MLV) containing muramyl dipeptide (MDP) at a minimum dose of approximately 0.6 micrograms or less than a 10-fold dilution of cellfree culture supernatants from mitogen-stimulated F-344 rat lymphocytes rich in macrophage-activating factor (MAF) activity. Neither MAF at dilutions exceeding 1/10 nor MDP at doses lower than approximately 0.6 micrograms activated AM in situ to become tumor cytotoxic. The combination of these agents at subthreshold amounts (MAF 1/20, MDP 0.3 microgram), however, activated AM to significant levels of cytotoxicity. The synergism between MAF and MDP encapsulated in liposomes was also observed in therapeutic studies of mice bearing well established, spontaneous lung and lymph node metastases. Multiple i.v. injections of liposomes containing either 6.25 micrograms MDP or a 1/2 dilution of MAF resulted in the long-term survival (greater than 250 days) of 30% of the treated mice. Neither liposomes containing MAF at a 1/20 dilution nor MDP at doses lower than 0.6 microgram were therapeutically effective. Multiple injections of liposomes containing subthreshold amounts (MAF 1/20; and MDP 0.3 micrograms) of these agents, however, resulted in 50% survival in the treated group. These data allow us to conclude that the encapsulation of MAF and MDP within the same MLV is more efficient in inducing the destruction of metastases than either agent administered alone.
Immune serum against Anaplasma marginale initial bodies neutralizes infectivity for cattle.
Authors: Palmer G H , McGuire T C 
Published: December 2022

Abstract
The first demonstration of immune serum-mediated neutralization of Anaplasma marginale and identification of the involved surface antigens is presented. Anaplasma marginale initial bodies were purified from parasitized erythrocytes by using ultrasonic disruption and differential centrifugation. The initial bodies were morphologically intact, as determined by electron microscopy, were not agglutinated by anti-bovine erythrocyte sera, and were infective. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated minimal erythrocytic contamination in the purified initial bodies. Rabbit antisera against initial bodies completely neutralized the infectivity of purified initial bodies for splenectomized calves, whereas normal rabbit serum did not alter infectivity. Nine initial body proteins were surface radioiodinated by using lactoperoxidase, and five of these were precipitated by the neutralizing antibody (105,000, 86,000, 61,000, 36,000, and 31,000 apparent m.w.). The results demonstrate that initial body determinants capable of inducing neutralizing antibody are present. The identification of surface radiolabeled proteins immunoprecipitated by the neutralizing antibody provides candidates to be tested as protective immunogens in cattle.
Polyclonal activation of the murine immune system by an antibody to IgD. VII. Demonstration of the role of nonantigen-specific T help in in vivo B cell activation.
Authors: Finkelman F D , Smith J , Villacreses N , Metcalf E S 
Published: December 2022

Abstract
Previous studies from this laboratory have shown that the injection of mice with an affinity-purified goat antibody to mouse IgD (GaM delta) induces T-independent polyclonal increases in: 1) B cell DNA synthesis, and 2) expression of surface Ia antigen and receptors for T helper factors, 1 to 2 days after injection. In addition, T-independent polyclonal increases in B cell number and IgG1 secretion are observed 6 to 7 days after injection. The administration of normal goat IgG (GIgG) along with GaM delta has been shown to augment GaM delta-induced polyclonal IgG1 secretion. To obtain information about the characteristics of the T help that is required for polyclonal antibody production in this model system, we investigated: 1) the length of the period during which GaM delta must be present to induce day 7 polyclonal antibody production, and 2) the kinetics of the induction of splenic T cell DNA synthesis. We found that GaM delta can be neutralized 3 days after injection by the administration of IgD without decreasing day 7 polyclonal IgG1 secretion, as long as mice are given GIgG at the time that GaM delta is neutralized. In contrast, polyclonal IgG1 secretion is greatly inhibited if GaM delta is neutralized 1 to 2 days after injection or if GaM delta is neutralized 3 days after injection, but GIgG is not administered at this time. Because GIgG can stimulate activated GIgG-specific T cells to secrete helper factors, but, unlike GaM delta cannot focus GIgG-specific T help polyclonally onto B cells, these findings suggest that nonspecific T help, rather than antigen-specific T help, is required in this system after day 3 for the induction of polyclonal IgG1 secretion. Determination of the kinetics of the induction of T cell DNA synthesis in this system by in vivo [3H] thymidine incorporation studies, as well as dual laser fluorescence-activated cell sorter analysis of T and B cell DNA content, indicate that T cells are induced to synthesize DNA 2 days after GaM delta injection and reach plateau rates of DNA synthesis 3 days after injection. Taken together, the GaM delta neutralization experiments and DNA synthesis studies suggest that one reason that GaM delta is required for 3 days in this system is to allow maximal activation of GIgG-specific T cells, which when stimulated later by GIgG secrete nonantigen-specific helper factors that induce GaM delta-activated B cells to secrete IgG1.
Endogenous blood levels of corticosterone control the immunologic cell mass and B cell activity in mice.
Authors: del Rey A , Besedovsky H , Sorkin E 
Published: December 2022

Abstract
An inverse relation between endogenous levels of glucocorticoids and splenic mass and cellularity was detected. Decreased endogenous corticosterone blood levels result in an increased number of immunoglobulin-secreting cells in the spleen, a fact that cannot be attributed only to the expansion of the lymphoid cell mass. The opposite phenomenon was observed in animals with high corticosterone blood levels, which showed reduced numbers of immunoglobulin-secreting cells. It is concluded that endogenous glucocorticoid levels contribute to the control of B cell activity and possibly to the interaction of these cells with other immunologic cells.
Interactions between T lymphocyte subsets supported by interleukin 2-rich lymphokines produce acute rejection of vascularized cardiac allografts in T cell deprived rats.
Authors: Heidecke C D , Kupiec-Weglinski J W , Lear P A , Abbud-Filho M , Araujo J L , Araneda D , Strom T B , Tilney N L 
Published: December 2022

Abstract
A series of adoptive transfer studies were performed to define both the role of lymphocyte subpopulations and of lymphokines in the reestablishment of immunologic responsiveness towards vascularized organ allografts in T cell-deprived B rats. Acute rejection of otherwise indefinitely surviving cardiac allografts (10.9 +/- 2.9 days) occurred when sensitized T cells were adoptively transferred with a course of partially purified, lectin-free IL 2-conditioned medium (IL 2CM), whereas rats receiving T cells alone rejected their grafts at 19.8 +/- 4.6 days (p = 0.025). Rejection is mediated primarily by alloactivated T helper cells highly enriched for W3/25 phenotype. The relationship between the mean allograft survival time and the cell number transferred was of exponential order. In contrast to rejection occurring after the transfer of intact T cells, that produced by W3/25+ cells was independent of the administration of exogenous IL 2CM. W3/25+ T helper cells were also found to be less potent in mediating graft rejection than were whole T cells when limited cell numbers were transferred. The OX8+ T cytotoxic/suppressor cell subpopulation, even when supplied with a course of IL 2CM, was unable to bring about rejection, but induced transient graft enlargement in about 50% of the animals. Recombination of individual subsets caused acute rejection at a rate comparable to that of unseparated T cells when IL 2CM was supplied (10.8 +/- 1.0 days), in contrast to those rats which received the recombined inoculum in the absence of IL 2CM (16.8 +/- 2.2 days, p = 0.025). Lymphocyte migration studies revealed a more vigorous homing of OX8+ cells to the allograft as compared to W3/25+ cells. However, to produce maximal accumulation of transferred cells in the graft, both T cell subsets supplemented by lymphokines must be introduced together into T cell-deprived hosts.
An analysis of functional T cell recognition sites on I-E molecules.
Authors: Needleman B W , Pierres M , Devaux C A , Dwyer P N , Finnegan A , Sachs D H , Hodes R J 
Published: December 2022

Abstract
The recognition of I-E molecules by antigen-specific T cells was studied to determine if one or multiple topographic sites on the I-E molecules can function as restricting elements for T cells. A panel of 14 I-Ek-specific monoclonal antibodies (mAb) was used to inhibit T cell proliferation induced by antigens, the recognition of which was restricted by I-E-encoded determinants. These antibodies gave patterns of inhibition that were similar for three long-term antigen-specific T cell lines. Multiple distinct patterns of inhibition, however, were observed when a series of antigen-specific I-E-restricted T cell clones was studied. Differences were identified even among clones expressing apparently similar antigen specificities and MHC restriction. The observed inhibition by these antibodies appeared to be caused by specific steric or allosteric interference with T cell recognition of antigen and Ia. Based on the differences in patterns of inhibition, it was possible to infer the existence of distinct sites or conformations on the I-E molecule that are functionally involved in antigen-specific T cell recognition.
Isolation and characterization of an I-A-restricted T cell clone with dual specificity for poly(Glu60Ala30Tyr10) (GAT) and Mlsa,dl.
Authors: Jenkins M K , Melvold R W , Miller S D 
Published: December 2022

Abstract
We have isolated a BALB/c (H-2d, Mlsb) T cell clone (JTL-G12) specific for the synthetic polypeptide antigen poly(Glu60Ala30Tyr10) (GAT) in the context of self I-A determinants and for Mlsa,d antigens in the absence of GAT. JTL-G12 proliferation in response to GAT was mapped to the Kd, I-Ad subregions by using inbred H-2 congenic and recombinant strains. In addition, monoclonal antibody directed against I-Ad but not Kd or I-As determinants blocked JTL-G12 proliferation in response to GAT presented by syngeneic splenocytes, indicating I-A restriction. The Mls cross-reactivity of this clone was verified by using a panel of inbred strains bearing the Mlsa,b,c,d alleles and by using BXD recombinant inbred strains bearing the Mlsa allele or the Mlsb allele. All of the Mlsa BXD strains of the H-2d or H-2b haplotypes stimulated JTL-G12 in the absence of GAT, whereas all of the Mlsb BXD strains were nonstimulatory. This response pattern is in complete accordance with recognition of the Mlsa determinant encoded by Mls or closely linked loci on chromosome 1. JTL-G12 proliferation in response to GAT/I-Ad and Mlsa,d determinants could be blocked with a monoclonal antibody (GK1.5) directed against L3T4, a structure involved in class II major histocompatibility complex antigen recognition. These results suggest that antigen/class II responsiveness, Mls reactivity, and expression of L3T4 can be properties of a single T cell population.