bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further Studies on the Activation of Lymphocytes by Endotoxin Protein
Authors: Goodman Gail W. , Sultzer Barnet M. 
Published: December 2022

Abstract
Endotoxin protein, an outer membrane protein of Gram-negative bacteria associated with lipopolysaccharide endotoxin, has been found to be a potent activator of lymphocytes. In the absence of T lymphocytes and macrophages, endotoxin protein can stimulate murine B lymphocytes to synthesize DNA and produce antibodies of diverse specificities. This stimulation is greater than that obtained with two well known murine B cell activators, lipopolysaccharide endotoxin or PPD-tuberculin. Splenic lymphocytes from other species, such as rats, rabbits, and guinea pigs also proliferate when cultured with endotoxin protein. Of particular significance is the finding that endotoxin protein is an activator of human peripheral blood lymphocytes.
The Expression of Ia Antigenic Determinants on Macrophages Required for the in Vitro Antibody Response
Authors: Niederhuber John E. , Allen Paul , Mayo Laura 
Published: December 2022

Abstract
A subpopulation of antigen-presenting macrophages required for an in vitro antibody response to burro erythrocytes was deleted by pretreating the splenic macrophages with anti-Ia serum and complement (C). The in vitro response of the macrophage depleted T-B cell population could not be restored by the addition of macrophages resistant to anti-Ia antibodies and C (Ia-). The response of Ia- macrophages and the macrophage-depleted T-B cells was only reconstituted by the addition of Ia+ macrophages. Macrophages pretreated with anti-Ia antibodies restricted to react with determinants of one I subregion could not support the in vitro antibody response when added to cultures whose macrophages were pretreated with anti-Ia serum and C specific for the I-J subregion. These results confirmed that Ia determinants of the I-A, the I-E, and the I-C subregions were all expressed on the I-J+ macrophage required for an in vitro antibody response.
Interaction of Human Cells with Prostaglandins and Cyclic AMP Modulators
Authors: Trofatter Kenneth F. , Daniels Charles A. 
Published: December 2022

Abstract
The release of prostaglandins (PG) has been incriminated in exacerbations of latent herpes simplex virus (HSV) infections in humans, but the mechanism(s) by which PG could precipitate a recurrence has not been adequately explored. In this study we determined the effect of PG-A1, B1, E1, E2, F2α, and other cAMP elevating agents had on complement (C)mediated lysis and antibody-dependent cell-mediated cytolysis (ADCC) of HSV-infected human fibroblasts (HuF). C-lysis was not inhibited by PG, phosphodiesterase inhibitors, or dibutyryl-cAMP regardless of the concentrations of reagent, human antiHSV, or C that was incubated with the HuF. As determined by 51Cr release, human mononuclear leukocytes (MNL) were inhibited from mediating ADCC by PGE1 or E2 (≥0.1 µg/ml), PGF2α or A1 (≥1.0 µg/ml), PGB1 (10 µg/ml), isoproterenol (≥10-6 M), theophylline (≥10-3 M), methyl-isobutyl-xanthine (≥10-4 M), and db-cAMP (≥10-4 M). The inhibitory effect these reagents had on ADCC was removed by washing the cells and no adverse effect on viability was noted. Another quantitative ADCC assay, antibody-dependent suppression of plaque formation, also indicated that PGE2 inhibited MNL-mediated ADCC, and showed the reagent had no effect on virus growth in HuF. Except for the 1.0 µg/ml concentrations of PGF2α and A1, the inhibition of ADCC produced by PG was correlated with significant elevations of cAMP in the human MNL. Finally, experiments showed that as the concentration of PGE2 added to the cultures increased, there was a decrease in both the number of MNL attached to the HuF and the amount of ADCC obtained. Thus, the data indicated that PGE2 inhibited cytolysis by interfering with attachment of the effector MNL to the antibody-coated target cells. In summary the studies support the proposition PG could cause exacerbation of HSV disease in patients by suppression of ADCC.
3H-5-Uridine Incorporation by Small Lymphocytes from Transplantation-Tolerant and Tolerance-Reversed Rats
Authors: Dennison David K. , Clancy John 
Published: December 2022

Abstract
The level of 3H-5-uridine (3H-Urd) incorporation by rat small lymphocytes (SL) taken from donors tolerant (T) or previously T to an allogeneic skin graft was monitored. DA rats were made T to Lewis (L) alloantigens by the injection at birth of semiallogeneic DA/L F1 bone marrow cells. Eight to 12 weeks after birth, allogeneic L skin was transplanted to the T rats. Animals accepting their skin graft for &gt;100 days were either killed and 3H-Urd incorporation by SL from mesenteric lymph nodes (MLN) and spleen (SPL) was monitored, or the rats were injected with syngeneic DA MLN and SPL cells to abolish tolerance. Tolerance-abolished (TA) animals were killed and 3H-Urd incorporation was monitored autoradiographically at intervals before and after skin graft rejection. The level of graft-vs-host (GVH) reactivity of MLN cells from all T and TA rats was evaluated in a local popliteal lymph node GVH assay. T animals demonstrated a markedly depressed GVH reactivity when compared with control animals. Also, MLN SL from T rats autoradiographically exhibited 14.23 grains/SL, 226% above the average of 6.32 grains/SL observed in MLN SL from control animals. 3H-Urd incorporation by splenic SL from T rats was likewise elevated above control animals, representing a 221% increase. There was no increase in IgM+ cells in T vs. control animals. After i.v. injection of normal DA LN and SPL cells, the allogeneic grafts were rejected at 20 ± 2 days. However, from 15 to 21 days after the injection of syngeneic cells, the TA rat LN and SPL SL incorporated 3H-Urd at levels intermediate between those of T and control animals, but exhibited a level of incorporation not significantly different from controls 24 days after syngeneic cell injection. In addition, GVH reactivity of MLN cells taken from a T animal injected with syngeneic cells was restored gradually over a time period of &gt;24 days. The fact that 3H-Urd levels are elevated in T animals indicates that an active phenomenon is related to the T state. The decrease in uridine incorporation during tolerance reversal provides further support for a metabolic change during tolerance that is different from that found in control animals.
The Activation of Guinea Pig T Lymphocytes by Anti-β2-Microglobulin Serum
Authors: Yamashita Uki , Lögdberg Lennart , Berggård Ingemar , Shevach Ethan M. 
Published: December 2022

Abstract
In order to study further the role of β2-m in the regulation of the immune response, we have examined the effects of a goat anti-guinea pig β2-m serum on a number of T lymphocyte functions in vitro. Anti-β2-m serum produced a marked inhibition of the response of peritoneal exudate T cells to antigen and mitogen stimulation. Surprisingly, a marked activation of lymph node T lymphocyte proliferation was observed in the absence of antigen or mitogen stimulation. This stimulatory effect of anti-β2-m serum was shown to be specific for β2-m and required the presence of macrophages. The T cell proliferative response induced by anti-β2-m could not be blocked by antisera to the antigens of the guinea pig MHC. These studies suggest that β2-m may play some critical role in the immune response at the level of T cell activation.
Nonspecific Activation of Murine Lymphocytes
Authors: Goodman Michael G. , Weigle William O. 
Published: December 2022

Abstract
The role of cellular interaction in the mitogenic activation of B and T lymphocytes by 2-mercaptoethanol was studied in cultures of C3H/St spleen cells. It has previously been shown that both B cell-enriched and T cell-enriched populations are capable of mitogenic response to 2-ME. In the present communication it is demonstrated that reactivity to 2-ME cannot occur when cells are cultured below a minimal permissive cell concentration. This permissive range exhibits an optimum beyond which responsiveness per cell declines. Analysis of the kinetic profile of cells cultured at different densities indicated that this observation was not the result of differential kinetics. When B and T cell-enriched populations were mixed in culture, 2- 3-fold enhancement of the mitogenic response to 2-ME resulted. Optimal responsiveness was shown to occur in the region of moderate T cell excess. Because the B cell-enriched population contained substantially more macrophages than did the T cell-enriched population, synergy was evaluated after the B cells had been depleted of macrophages. The collaborative interaction between B and T cells nevertheless remained intact. Furthermore, when macrophage-poor T cell populations were supplemented with additional macrophages, no synergistic response was observed. Treatment of the B cell-enriched population with anti-immunoglobulin antiserum plus complement completely abrogated the synergistic interaction between the two cell types. Similarly, treatment of the T cell-enriched populations with anti-thymocyte serum plus complement abolished synergy. Thus, these experiments confirm the identity of the collaborating lymphocyte types. T cells were furthermore shown to be capable of providing help to B cells in their response to poly-clonal B cell activation. The implications of these observations are discussed both with regard to the mechanism of activation of lymphocytes by 2-ME and with regard to the role of T cells in the process of polyclonal B cell activation.
Genetic Studies in NZB Mice
Authors: Raveche Elizabeth S. , Tjio Joe H. , Steinberg Alfred D. 
Published: December 2022

Abstract
These studies were performed to test the previously advanced hypothesis that the antibody response to ssDNA is controlled by an X-linked immune response gene. The antibody response to single-stranded DNA (ssDNA) complexed to MBSA was studied in NZB, DBA/2, F1 reciprocal hybrids, and backcross mice. We found that the anti-ssDNA response was not linked to genes located on the X chromosome, but rather that anti-ssDNA production was regulated by sex hormones. Reciprocal F1 hybrid males with either an NZB or a DBA/2 X chromosome were low responders; however, either castration or castration plus estrogen implants significantly increased the amount of antibody produced. Testosterone implants were immunosuppressive in both females and males. Backcross studies suggested that the ability to respond to ssDNA is inherited as an autosomal dominant trait that is further regulated by sex hormones.
Control studies were performed in hybrids of the CBA/N strain, which has a well established X-linked defect in the ability to respond to a variety of thymic independent antigens including polyriboinosinic·polyribocytidylic acid (rI·rC). F1 hybrid males that received the CBA/N X chromosome were low-responders to rI·rC despite the hormonal status of the animal. On the other hand, females were high responders to rI·rC but testosterone implants in females decreased the amount of antibody produced.
These studies indicate that it is possible to separate sex hormone effects from X-linked genetic effects on immune responses. We found that the response to ssDNA is controlled by sex hormones but not an X-linked immune response gene.
Many Bacterial Species Bind Human IgD
Authors: Forsgren Arne , Grubb Anders O. 
Published: December 2022

Abstract
Forty-four bacterial strains belonging to 19 species were tested for their IgD-binding capacity by incubation with radiolabeled human IgD. A high binding of IgD to Neisseria catarrhalis and Hemophilus influenzae and a moderate binding of IgD to streptococci of the groups A, C, and G were found. Two strains of N. catarrhalis were tested for their ability to bind selectively the IgD in normal pooled serum and in three serum samples with IgD M components and were found to possess this property. Binding studies with radiolabeled IgD Fab and Fc fragments indicated that the binding mainly but not exclusively involves the CH1 region of the IgD molecule.
Cytotoxicity by Cultured Human Lymphocytes: Characteristics of Effector Cells and Specificity of Cytotoxicity
Authors: Ortaldo J. R. , Bonnard G. D. , Kind P. D. , Herberman R. B. 
Published: December 2022

Abstract
The specificity and the cells involved in natural cytotoxicity against tumor cells by fresh normal human peripheral blood mononuclear leukocytes have been extensively examined. Recently we have observed that removal of Fc receptor-positive cells from peripheral blood mononuclear leukocytes on day 0 removed all natural cytotoxic activity against K-562 (a myeloid leukemia cell line that is particularly susceptible to natural cytotoxicity) but after in vitro culture for 7 days, cytotoxic activity against K-562 had regenerated to near its original level.
In the present study, we examined the specificity of the cytotoxicity of both fresh and cultured peripheral blood mononuclear leukocytes against a panel of target cells susceptible to natural killing and the characteristics of the cultured effector cells. By testing various donors against a checkerboard panel of labeled target and cold target inhibitor cells, it was found that the reactivity after culture was similar to that seen on day 0. Small variation in rank order of the level of inhibition was observed in most experiments, but none of the reactivity patterns of the donor lymphocytes demonstrated major changes after culture. Furthermore, the surface characteristics of the effector cells before and after culture were similar with regard to surface immunoglobulin, Fc receptors, complement receptors, sensitivity to trypsin and to specific anti-T antiserum. However, the cultured effector cells did have some distinctive characteristics, rosetting less with sheep red blood cells, adhering to some extent to rayon wool, and being partially sensitive to an anti-Ia-like antiserum. These features may indicate that the cultured cells are at a different stage of differentiation than in vivo generated natural killer (NK) cells. These results indicate that the natural cytotoxicity of human lymphocytes and the reactivity of cultured cells are mediated by similar effector cells, i.e., NK cells, and are directed against similar specificities.
Studies of the Mechanisms for the Induction of in Vivo Tumor Immunity
Authors: Igarashi Tsuyoshi , Rodrigues Dennis , Ting Chou-Chik 
Published: December 2022

Abstract
The effect of macrophages on the induction of the cell-mediated cytotoxicity against a leukemia in a syngeneic system was investigated. The addition of exogenous peritoneal cells from normal C57BL/6 mice enhanced the in vitro secondary cell-mediated cytotoxic response of both spleen and lymph node cells as responding cells against syngeneic FBL-3 leukemia. Peritoneal phagocytic macrophages seemed to be responsible for the enhancement. No inhibitory effect was demonstrated by the addition of peritoneal macrophages at a concentration as high as 20%, whereas the primary cytotoxic allograft response was significantly suppressed. In the present studies, there was no absolute restriction of macrophage-T cell interaction by an H-2 barrier. Supernatants of peritoneal macrophage cultures also enhanced this cell-mediated cytotoxic response. There was no difference between the effects of syngeneic or allogeneic peritoneal macrophage culture supernatants.
Formation of Thromboxane B2 and Hydroxyarachidonic Acids in Purified Human Lymphocytes in the Presence and Absence of PHA
Authors: Parker Charles W. , Stenson William F. , Huber Mary G. , Kelly James P. 
Published: December 2022

Abstract
The metabolism of exogenous and endogenous [14C] arachidonc acid was studied in purified human peripheral blood lymphocytes carefully freed of contaminating platelets. Formation of products co-migrating in a number of different solvent systems with 5-hydroxyarachidonic acid (5-HETE), thromboxane B2 (TB2), prostaglandins and probably 12-hydroxyarachidonic acid (12-HETE) was demonstrated. In cells prelabeled with [14C] arachidonic acid, phytohemagglutinin (PHA) produced substantial (3.5- to 12-fold) increases in 5-HETE, 12-HETE, and TB2 radiolabeling. The metabolism of exogenous [14C] arachidonic acid was much less affected by PHA. Since PHA releases cell-bound arachidonic acid, it appears that the response involving endogenous label is due to increased availability of free arachidonic acid rather than induction of arachidonic acid-metabolizing enzymes. Various inhibitors of arachidonic acid metabolism exerted similar effects in lymphocytes to those described previously in other tissues providing a possible basis for interpreting their inhibitory effects on mitogenesis, described in the preceding paper.
In Vivo Generation of Hapten-Specific Killer T Cells without Elimination of Suppressor Cells
Authors: Butler Larry D. , Battisto Jack R. 
Published: December 2022

Abstract
We have provided evidence to demonstrate that hapten-specific killer cells can be generated in vivo toward hapten-conjugated syngeneic splenic cells. The critical aspect is to provide an auxiliary cellular antigenic stimulus in addition to the hapten-conjugated syngeneic cells. In our experiments this stimulus was CBA/J splenic cells that possess Mls disparate but H-2 compatible antigens with C3H/HeN hosts. The Mls antigen has been shown by others to activate helper T cells in vitro to synthesize KAF, a signal that prekiller cells require besides target antigen. Killer cells (shown to be T cells) as well as helper T cells were found to be derived from the C3H host. Induction in the host animal of partial tolerance to the auxiliary cells possessing Mls antigen abrogated the response.
This system, besides providing a better understanding of the control mechanisms involved in the development of T killer cells in vivo, points to a way in which the latter may be generated toward haptenic moieties on syngeneic cells without the necessity for eliminating suppressor cells. The latter principle may prove highly useful in certain clinical situations.
Defective Tumoricidal Capacity of Macrophages from A/J Mice
Authors: Boraschi Diana , Meltzer Monte S. 
Published: December 2022

Abstract
Macrophages from A/J mice fail to develop tumoricidal activity after any of several in vivo or in vitro treatments that activate cells from C3H/HeN mice. Peritoneal macrophages from A/J mice treated i.p. with viable Mycobacterium bovis, strain BCG, killed Corynebacterium parvum, or pyran copolymer fail to develop in vitro tumoricidal activity; varying the numbers of macrophages from treated mice added to target cells, or the dose and time of treatment, or the treatment schedule of these in vivo activation stimuli did not evoke cytotoxic activity. Moreover, cytotoxic activity by macrophages from A/J mice was not observed with any of four target cell lines derived from three different mouse strains. In vitro treatment of peritoneal exudate macrophages from A/J mice with lymphokine-rich supernatants, bacterial endotoxins, or T cell mitogens was also ineffective; varying the numbers of treated macrophages added to target cells, the dose of in vitro activation stimuli, or the time of treatment did not evoke cytotoxic activity. Thus, A/J mice exhibit a profound defect in macrophage tumoricidal capacity to both in vivo and in vitro activation stimuli over a wide range of experimental conditions.
Macrophage-Lymphocyte Clusters in the Immune Response to Soluble Protein Antigen In Vitro
Authors: Braendstrup Otto , Werdelin Ole , Shevach Ethan M. , Rosenthal Alan S. 
Published: December 2022

Abstract
We have assessed the genetic restrictions on physical interactions between macrophages and central lymphocytes and between central and peripheral lymphocytes in antigen-specific macrophage-lymphocyte clusters with respect to I-region differences of inbred strains 2 and 13 guinea pigs. When using lymphocytes from guinea pigs immunized with DNP-OVA or DNP-GL in CFA, the antigen-specific interaction between central lymphocyte and macrophage requires that both cells be derived from animals syngeneic at the I-region of the major histocompatibility complex. In studies using antigens, the response to which is under the control of MHC-linked Ir genes, macrophages from the responder, but not from the nonresponder parental strain support cluster formation with responder × nonresponder F1(2 × 13) T cells. In contrast, the physical interactions between central and peripheral T lymphocytes are not restricted by the I-region of the MHC and the peripheral lymphocyte need not be from an animal immune to the antigen used to drive macrophage central lymphocyte interactions.
Hypocomplementemia Associated with Naturally Occurring Lymphosarcoma in Pet Cats
Authors: Kobilinsky Lawrence , Hardy William D. , Day Noorbibi K. 
Published: December 2022

Abstract
Eighty cats were classified by indirect immunofluorescence and histologic diagnosis into four categories: normal, feline leukemia virus (FeLV) infected; normal noninfected; lymphosarcoma-FeLV infected; lymphosarcoma, no FeLV present. All viremic cats with lymphosarcoma were found to be hypocomplementemic and activation of the complement system had occurred via the classical pathway. Sera of cats with lymphosarcoma in the absence of FeLV had varying levels of total hemolytic complement (TCH50) ranging from normal to hypocomplementemic. Approximately 50% of the cats that were viremic but histologically and clinically free of disease had TCH50 levels within normal range, and the remainder exhibited varying degrees of hypocomplementemia.
PPD-Induced Immunoglobulin Production in Human Peripheral Blood Lymphocytes
Authors: Nishikawa Shin-Ichi , Hirata Takeo , Nagai Tomoko , Mayumi Mitsufumi , Izumi Takateru 
Published: December 2022

Abstract
The ability of PPD to induce Ig production in human PBL was investigated. PPD proved to be a good B cell activator for inducing polyclonal Ig production in PBL from healthy Japanese. Comparative studies of this response with PWM-induced Ig production showed that the cellular mechanisms involved in the two responses were different. First, PBL from an atypical individual with a deficient IgM production to PWM responded normally to PPD with IgM production as well as IgG production. Secondly, in IgG production, the effects of the two mitogens (PPD and PWM) were additive.
An analysis of the cellular requirements in PPD-induced Ig production clearly demonstrated that T cells played a role in this response as well as in the PWM-induced response. However, the head-to-head comparative study on the titration curves of helper T cells in the two responses showed that PWM-induced helper activity was 2 to 5 times more effective than PPD-induced helper activity. Moreover, PPD-induced helper activity was shown to be more sensitive to ionizing radiation than was PWM-induced helper activity. Thus, this system of PPD-induced Ig production may provide a useful tool for understanding the human antibody production system as well as the PWM-induced response.
Regulation of IgE Antibody Production by Serum Molecules
Authors: Katz David H. , Bargatze Robert F. , Bogowitz Cheryl A. , Katz Lee R. 
Published: December 2022

Abstract
Two biologically active serum molecules manifesting precisely opposite biologic effects, both of which are selective for IgE antibody synthesis, can be detected in the serum and ascites fluids of CFA-immune mice. One activity, described previously, is suppressive and hence termed suppressive factor of allergy (SFA); the other, reported for the first time herein, is enhancing and has been termed enhancing factor of allergy (EFA). The ability to detect one vs the other activity requires certain special manipulations such as different doses of low dose x-irradiation. Conclusive evidence for the existence of two distinct factors mediating these two opposing biologic effects was obtained in studies demonstrating that affinity chromatography on concanavalin A-Sepharose segregated the two molecular entities. Thus, SFA binds poorly or not at all to Con A-Sepharose, whereas EFA binds to Con A and can be recovered in the eluate eluted with the competitive sugar α-methyl-D-glucopyranoside.