bluuebunny/crossref_metadata_2025 huggingface dataset:
SURFACE MARKERS ON HUMAN T AND B LYMPHOCYTES
Authors: Jondal M. , Holm G. , Wigzell H.
Published: June 2004

By using the two criteria (a) high density of immunoglobulin determinants on the cell surface and (b) presence of receptors for C'3 on the cell surface for defining bone marrow-derived lymphocytes, it is indirectly shown that all or at least a major population of human thymus-derived lymphocytes under certain conditions will form nonimmune rosettes with sheep red blood cells (SRBC). Almost all thymocytes tested from two different donors formed rosettes. The SRBC rosettes are not formed by virtue of immunoglobulin receptors and form only around living cells. Positive bivalent ions are required for rosette formation since EDTA will block rosette formation. Sodium iodoacetate will also block rosette formation demonstrating the dependence on an intact glycolytic pathway. Rosette formation is temperature dependent and will not appear at 37°C. Trypsin treatment of lymphocytes will abolish their SRBC-binding ability which cannot be restored by treating them with fresh donor serum or fetal calf serum, but which will reappear after culturing the lymphocytes. It is suggested that these rosettes are formed by a rapidly released or metabolized receptor substance on the living cell surface which behaves as a trypsin-sensitive structure produced by the cells themselves.
SPECIFICITY OF THE INFLAMMATORY RESPONSE IN VIRAL ENCEPHALITIS
Authors: McFarland Henry F. , Griffin Diane E. , Johnson Richard T.
Published: June 2004

The viral-induced perivascular inflammatory response in Sindbis virus encephalitis of mice was shown to be immunologically specific. Mice were inoculated intracerebrally with Sindbis virus, and 24 hr later a single dose of cyclophosphamide was given which ablated the inflammatory response. 3 days after virus inoculation, cells and/or sera from specifically and nonspecifically sensitized donor mice were given, and the inflammatory reactions, virus content, and antibody response of recipients were examined 5 days later.

Reconstitution of the viral inflammatory response required virus-specific sensitized lymph node cells and was enhanced when these lymph node cells were combined with bone marrow cells. Reconstitution was not achieved with Sindbis virus immune serum even when combined with nonspecifically sensitized cells. Combination of immune serum with Sindbis virus-sensitized cells did not produce an accentuation of the reaction.

In distinction, reconstitution of the inflammatory reaction surrounding the stab wound was reconstituted with bone marrow cells from mice inoculated with Sindbis virus or control antigens.

Reconstitution of the perivascular reaction was associated with a reduction in brain virus content. Although the transfer of Sindbis virus-sensitized lymph node cells and bone marrow cells resulted in the limited production of neutralizing antibody in the immunosuppressed recipient, the reduction in virus was significantly greater with the transfers of Sindbis virus-sensitized lymph node cells than with the passive transfer of immune serum alone.
MECHANISM OF RECOVERY FROM SYSTEMIC VACCINIA VIRUS INFECTION
Authors: Worthington M. , Rabson A. S. , Baron S.
Published: June 2004

Administration of Cytoxan in doses capable of inhibiting both humoral and cellular immunity markedly potentiated primary systemic vaccinia virus infection in mice. Immunosuppressed mice did not form neutralizing antibody to vaccinia virus and had a prolonged and more severe viremia than nonimmunosuppressed control mice. Passive transfer of physiologic amounts of neutralizing antibody late in the course of infection, at a time when nonimmunosuppressed mice had similar levels of serum antibody, largely reversed the effect of Cytoxan on vaccinia virus infection. Transfer of 100 million immune spleen cells was much less effective than antibody in reversing the effect of Cytoxan on vaccinia virus infection, and mice receiving these cells did make some antibody. Serum interferon levels were not affected by Cytoxan. The results suggest an essential role for humoral antibody, but not for cellular immunity, in recovery from primary vaccinia virus infection in the mouse.
DELETION OF HAPTEN-BINDING CELLS BY A HIGHLY RADIOACTIVE 125I CONJUGATE
Authors: Golan Dov Theo , Borel Yves
Published: June 2004

Exposure of normal mouse spleen cells in vitro to highly 125I-labeled dinitrophenyl (DNP)-protein carrier conjugates specifically inactivated cells able to mount an immune response to that hapten after in vivo challenge. The deletion was hapten specific and independent of the radioactive carrier to which the hapten was bound. DNP-binding cells were inactivated by radioactivity that was not part of the hapten, but was solely confined to the carrier moiety. The deletion of the anti-DNP response lasted 2–3 wk and could be specifically inhibited.
LACK OF DISTINCTIVE SURFACE ANTIGEN ON CELLS TRANSFORMED BY MURINE SARCOMA VIRUS
Authors: Strouk Vladimir , Grundner Gertrud , Fenyö Eva Maria , Lamon Ed , Skurzak Henryk , Klein George
Published: June 2004

Some murine sarcoma virus (MSV)-transformed mouse 3T3 cells contain the MSV genome in the absence of infectious helper murine leukemia virus (MuLV) and MSV production.

These cells, designated S+L- (sarcoma positive, leukemia negative), were analyzed for the presence of a possible MSV-determined membrane antigen by the mixed hemadsorption test and in vitro lymphocyte cytotoxicity assay. Two different serological approaches were used: (a) isoantibody-free sera were obtained by immunizing with MSV of syngeneic origin or by allowing primary, autologous MSV sarcomas to regress, or (b) alloantisera obtained by immunizing C57BL mice with S+L- cells were absorbed with the corresponding nontransformed 3T3 cells until all activity against 3T3 had been removed.

While MuLV-superinfected S+L- cells and a culture line of an MSV sarcoma known to produce both MSV and MLV were highly reactive, normal 3T3 and S+L- cells were negative. Similarly, lymph node cells from MSV immune mice or rats did not kill S+L- cells, although they were cytotoxic against target cells known to carry MuLV-associated antigens. Thus, the present study gives no positive evidence for the existence of any MSV-induced new surface antigen in the transformed target cell, known to carry the viral genome.
ANTIGEN RECOGNITION AND THE IMMUNE RESPONSE
Authors: Alkan Sefik S. , Bush Maurice E. , Nitecki Danute E. , Goodman Joel W.
Published: June 2004

The low molecular weight compound L-tyrosine-azobenzenearsonate (RAT) induces a cellular immune response in guinea pigs. The contribution of the side chain of tyrosine to the immunogenicity of RAT and the structural requirements at that position for immunogenicity were assessed by synthesizing a series of analogs of RAT containing modifications in the side chain of tyrosine and employing them as immunogens. Removal of either the carboxyl or amino group did not markedly affect immunogenicity, measured by the induction of delayed cutaneous sensitivity, whereas deletion of both completely abolished it. However, a charged group was not required since side chains containing a polar hydroxyl group could substitute for chains bearing an amino or carboxyl group. The size of the side chain exerted a pronounced influence; the charged or polar substituent had to be extended from the phenolic ring by at least two carbon atoms in order to confer immunogenicity.
RESPONSIVENESS OF GERMFREE MICE IN MIXED LEUKOCYTE CULTURE
Authors: Widmer Michael B. , Sondel Paul M. , Bach Fritz H.
Published: June 2004

Conventional (cv) and germfree (gf) mice are able to give a good proliferative response to allogeneic cells in the mixed leukocyte culture (MLC) test, while the response to xenogeneic stimulating cells has been in question. Previous studies by others have suggested only a low MLC response in cv animals and none in gf ones. We have found that both cv and gf animals can give a good MLC response to xenogeneic as well as allogeneic cells. These findings are of importance for our understanding of both MLC stimulation and response.
ANTIGEN BINDING AND CAPPING BY LYMPHOCYTES OF GENETIC NONRESPONDER MICE
Authors: Dunham Edward K. , Unanue Emil R. , Benacerraf Baruj
Published: June 2004

Radioautographic study of the binding of GAT-125I to spleen cells of genetic responder and nonresponder mice demonstrates that among mice not injected with antigen all strains have approximately the same number of antigen-binding cells; after injection with antigen the number of antigen-binding cells increases in responders but not in nonresponders. Nonresponders are shown to make antibody after injection with GAT complexed with an immunogenic carrier, demonstrating the presence of potentially functional B cells in responders and nonresponders alike. When incubated in the warm, antigen-binding cells of both responders and nonresponders concentrate antigen at one pole of the cell, forming caps.
REACTIVITY OF LYMPHOCYTES FROM GERMFREE RATS IN MIXED LEUKOCYTE CULTURE AND IN GRATT-VERSUS-HOST REACTION
Authors: Nielsen H. E.
Published: June 2004

The reactivity of lymphoid cells from germfree and conventional CDF rats were compared in mixed leukocyte culture (MLC) with both allogeneic rat leukocytes and with human leukocytes as stimulating cells, and in a graft-versus-host (GVH) assay. There was no difference between germfree and conventional rats in any of these systems. Furthermore, the increase in GVH activity after specific immunization against a strong histocompatibility antigen was small in both cases. The findings are incompatible with the hypothesis that the high proportion of antigen-sensitive cells against strong histocompatibility antigens is caused by cross-reactions between microbial antigens and histocompatibility antigens.
THE ALLOGENEIC EFFECT IN INBRED MICE
Authors: Osborne David P. , Katz David H.
Published: June 2004

The administration of allogeneic lymphoid cells to 2,4-dinitrophenyl keyhole limpet hemocyanin (DNP-KLH)-primed mice prepares such recipients for markedly enhanced secondary anti-DNP antibody responses to a DNP conjugate of a heterologous carrier. This allogeneic effect phenomenon, reflecting the development of a graft-versus-host (GVH) reaction, was first described in guinea pigs and has been extended in the present studies to inbred mice. The expression of the allogeneic effect in mice is dependent upon critical factors such as the number and route of administration of allogeneic cells, the time interval between cell transfer and secondary challenge, and the strength of histocompatibility differences between the donor and the host. The transient GVH reaction established by the transfer of allogeneic cells obviates the requirement for carrier-specific helper T cells in secondary anti-DNP responses, as evidenced by the ability to elicit such responses with DNP-D-GL, a substance which presumably does not stimulate effective T cell helper function. These studies also demonstrate that primed B cells which are not an integral part of the active GVH reaction fail to produce enhanced levels of antibody.
MECHANISM OF ACTION OF MIGRATION INHIBITORY FACTOR (MIF)
Authors: Leu Richard W. , Eddleston A. L. W. F. , Hadden John W. , Good Robert A.
Published: June 2004

The initial interaction between migration inhibitory factor (MIF) and the guinea pig alveolar and peritoneal macrophage was studied. MIF-containing supernatants were generated from sensitized lymph node lymphocytes obtained from guinea pigs immunized with bovine gamma globulin in complete Freund's adjuvant. MIF-containing supernatants were markedly inhibitory for the migration of the peritoneal macrophage but had no effect on the alveolar macrophage. A linear relationship was observed between per cent inhibition of migration and serial twofold dilution of supernatant. Reexpressed in arbitrary MIF units, this relationship reflects a dose-response relationship with saturation characteristics. Pulse exposure of peritoneal macrophages to MIF resulted in adsorption of MIF onto both viable and nonviable cells with corresponding depletion of supernatant MIF. The alveolar macrophage did not adsorb MIF. Pulse adsorption of MIF onto the peritoneal macrophage is dependent on time, temperature, and cell number. Pretreatment of the cells with proteolytic enzyme prevents the adsorption of MIF while leaving migration unaffected. These observations support the existence of a specific cell surface receptor for MIF. The existence of such a receptor provides selectivity of immune modulation of macrophage populations by lymphocytes in delayed hypersensitivity reactions.
IDIOTYPIC DETERMINANTS OF IMMUNOGLOBULIN M DETECTED ON THE SURFACE OF HUMAN LYMPHOCYTES BY CYTOTOXICITY ASSAYS
Authors: Wernet P. , Feizi T. , Kunkel H. G.
Published: June 2004

The complement-mediated cytotoxicity assay has been used to demonstrate surface immunoglobulin determinants on human peripheral blood lymphocytes. In two individuals with monoclonal serum IgM components, idiotypic antisera demonstrated similar components on a significant proportion of the peripheral blood lymphocytes.
SURFACE ANTIGENS OF IMMUNOCOMPETENT CELLS
Authors: Mond J. J. , Takahashi T. , Thorbecke G. J.
Published: June 2004

The effect of preincubation with anti-θ or anti-mouse immunoglobulin (Ig) and complement (C') on immune responsiveness of spleen cells from BALB/c mice immunized with sheep erythrocytes (SE) was investigated. Both treatments greatly depressed the remaining ability to produce a secondary response to SE in vitro.

Normal BALB/c spleen cells were far less effective in reconstituting the responses of such depleted cell populations than were much smaller numbers of untreated immune spleen cells. Thymus-derived cell (T cell) memory appeared early after immunization and showed specificity for the immunizing antigens.

Recombination of anti-Ig-treated with anti-θ-treated immune spleen cells resulted in virtually complete reconstitution of responsiveness. The presence of immunological memory in T cells and the nature of their surface receptors are discussed.
CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO
Authors: Feldmann Marc , Basten Antony
Published: June 2004

The role of soluble factors in cell collaboration was investigated by means of a tissue culture system in which populations of T and B cells were either incubated together or separated from each other by cell impermeable membranes. Histoincompatible T cells were found to augment antibody responses to both thymus-dependent and thymus-independent antigens, whether they were in contact with B cells or not. The properties of the factor released by the T cells in the allogeneic mixture were compared with those of the previously reported antigen-specific mediator found in syngeneic collaborative antibody responses. Unlike the latter, the factor made in allogeneic responses failed to display any degree of antigen specificity either in its induction or in its action, enhancing responses to all the antigens present in the cultures to a similar degree. It was of lower molecular weight than the antigen-specific factor, because it could pass through dialysis membranes as well as nuclepore membranes, whereas the antigen-specific factor could only penetrate nuclepore membranes. Furthermore, the factor made in allogeneic reactions had a different site of action. It acted directly on B lymphocytes, whereas the antigen-specific component acts through macrophages. Although antigen in the presence of the allogeneic factor did not initiate antibody production, it augmented responses once they had been induced by a matrix of antigenic determinants, either mediated by the antigen-specific factor or directly by a thymus-independent antigen. It was therefore considered to act at a later stage of the antibody response, probably as a nonspecific stimulator of immune B cell proliferation. Observations that the effect on the allogeneic factor are more pronounced 2 days after the beginning of the response are in keeping with this interpretation.
SPLENIC REPLENISHMENT OF SYNERGISTIC ABILITY TO BONE MARROW AND THYMIC CELLS OF NEONATALLY SPLENECTOMIZED CBA MICE
Authors: Bucsi R. A. , Borek F. , Battisto J. R.
Published: June 2004

Bone marrow (B) and thymic (T) cells taken from adult mice that had been splenectomized within 24 hr of birth showed an inability to cooperate in the IgM response to sheep red blood cells. The defect in collaborative capacity was apparent in both sets of cells, but appeared to be more pronounced in the T cell population. Splenectomy performed at various neonatal intervals indicated that if removal of the spleen were delayed until 6 days after birth, B and T cells of the adult showed a 60% restoration in cooperation. Replenishment of the synergistic ability after neonatal splenectomy could be achieved by injecting spleen cells immediately after spleen removal or 2 months postsplenectomy.
EXPERIMENTAL ARTERIOSCLEROSIS
Authors: Stemerman Michael B. , Ross Russell
Published: June 2004

Arteriosclerotic lesions have been produced in monkeys (Macaca nemestrina) by selective removal of the vascular endothelium with an intra-arterial balloon catheter. Immediately after de-endothelialization a platelet layer covers the denuded area. This thrombus is gradually removed and by 7 days the vessel appears to be largely reendothelialized. Beginning at day 4, smooth muscle cells undergo modification and migrate through fenestrae in the internal elastic lamina into the intima where they proliferate. By 28 days, the intimal lesion consists of multiple layers of smooth muscle cells surrounded by collagen and elastic fibers and basement-like material. After 3 months the lesions are markedly hyperplastic and contain new extracellular connective tissue elements. In contrast, with no further injury after 6 months the lesion has decreased markedly in size suggesting that it may be reversible in the absence of continued endothelial injury. The importance of endothelial "injury" exposing medial smooth muscle to plasma constituents may be the principal factors associated with the migration and proliferation of the smooth muscle cells into the intima resulting in the lesion. The smooth muscle cells do not contain lipid. The similarities of this lesion to the fibromusculo-elastic lesion or preatherosclerotic intimal hyperplasia in man makes it a useful model for the further study of atherosclerosis.
REGULATION OF LYMPHOCYTE RESPONSES IN VITRO
Authors: Yoshinaga Masaru , Yoshinaga Aiko , Waksman Byron H.
Published: June 2004

DNA synthesis of normal rat spleen cells in response to endotoxin increases markedly if adherent cells are first removed from the cell suspension. Addition of small numbers of purified macrophages to the cultures restores the response to a low level. T-deprived cells show these effects in very much lesser degree. Large numbers of macrophages completely suppress the response of both normal and T-deprived spleen. We conclude that two mechanisms of suppression are at work: a direct effect of macrophages and a macrophage-dependent "suppressor T cell" effect.
MOUSE THYMUS-INDEPENDENT AND THYMUS-DERIVED LYMPHOID CELLS
Authors: Matter A. , Lisowska-Bernstein B. , Ryser J. E. , Lamelin J.-P. , Vassalli P.
Published: June 2004

The ultrastructural features of B-, T-, and surface Ig(sIg)-bearing cells have been studied on cell suspensions from lymphoid organs of mice at different stages of immunization. The cells were identified by exposure to rabbit antibodies against mouse-specific lymphocyte antigens (MSLA) or brain-associated θ antigen (BAθ) for T cells, mouse-specific bone marrow-derived lymphocyte antigens (MBLA) for B cells, and mouse Ig for sIg-bearing cells. The rabbit antibodies fixed on the cell surfaces were detected by peroxidase-labeled sheep anti-rabbit Ig antibodies or by a "bridge" technique using southern bean mosaic virus or bacteriophage T4 as the final markers. In some experiments, short-lived lymphoid cells were labeled in vivo with repeated tritiated thymidine and the ultrastructural detection of their surface antigens was combined with radioautography.

MBLA+ lymphoid cells showed a whole range of ultrastructural patterns. Most were small and medium-sized lymphocytes with a clear cytoplasm containing mono- and polyribosomes, but they comprised also blasts and large cells with various amounts of endoplasmic reticulum, as well as plasma cells at different stages of maturation. sIg-bearing cells appeared to be identical with MBLA+ cells, except that sIg was less easily detectable on large blasts, and only very rarely observed on plasma cells. MSLA+ and BAθ+ cells fell into three categories. One of them (T1 cells) consisted of small to medium-sized lymphocytes with a clear cytoplasm and few organelles, mostly monoribosomes. A second consisted of large cells (T2 cells) characterized by numerous polyribosomes often in a "rosette"-like pattern, occasional dark, membrane-bound granules, and a developing "filamentous network." The third, very characteristic type, (T3 cells) was represented by dark small to medium-sized lymphocytes, usually containing large amounts of closely packed ribosomes and showing a striking accumulation of filamentous network, often condensed in large areas devoid of cell organelles. This filamentous network appeared to correspond to the cytochalasin B-sensitive system of microfilaments found in other cells and considered to be one of the contractile elements of the cell. The T3 lymphocytes showed frequently vesicles suggestive of a strong pinocytic activity, and assumed a variety of shapes, including uropods. Evidence is presented that T1 lymphocytes represent "virgin" T cells, T2 "activated," and T3 "differentiated" lymphocytes.
OCCURRENCE OF A THETA-LIKE ANTIGEN IN RATS
Authors: Douglas Tommy C.
Published: June 2004

A rat antigen system parallel to the mouse theta system has been described• All rat strains tested expressed an antigen cross-reactive with the θ-AKR specificity of mice while none cross-reacted strongly with θ-C3H. The rat antigen may be demonstrated by either absorption or direct complement-mediated killing of rat thymocytes. Patterns of organ distribution and developmental appearance in the nervous system of rats also parallel those previously reported for theta in mice.
STUDIES OF GENETIC TRANSMISSION OF MURINE LEUKEMIA VIRUS BY AKR MICE
Authors: Rowe Wallace P.
Published: June 2004

AKR mice, which regularly contain infectious murine leukemia virus, were mated with four Fv-1n strains of mice which show little or no expression of virus. F1, F2, and first and second backcross generation hybrids were tested for virus in tail tissue at 2 and 6 wk of age. The segregation data indicate that the AKR mouse contains two unlinked, autosomal, chromosomal loci, either of which suffices to induce detectable levels of infectious virus in Fv-1n progeny by 6 wk of age. One of the loci (tentatively referred to as V1) is on linkage group I, 25–30 map units from the locus for albino; the gene order tentatively appears to be N1-c-Hbb.
IN VITRO ACTIVATION OF CELLULAR IMMUNE RESPONSE TO GROSS VIRUS-INDUCED LYMPHOMA
Authors: de Landazuri Manuel Ortiz , Herberman Ronald B.
Published: June 2004

Spleen cells from W/Fu rats 40 days or more after immunization with a syngeneic Gross virus-induced leukemia were unreactive in direct cytotoxic assays. Incubation of these immune cells at 37°C for 12 hr or longer, in the absence of antigen, resulted in the appearance of specific cytotoxic reactivity. Other lymphoid cells from the immune rats also were activated upon in vitro incubation, but to a lesser extent. Experiments were performed to define the necessary conditions and the mechanism for the in vitro incubation. Activation was temperature dependent, occurring at 37°C but not at 4°C. Immune serum suppressed the activation, but normal rat serum also had some inhibitory activity. Passage of immune cells through a nylon column, before preincubation, prevented activation. In contrast, exposure to nylon after preincubation did not remove cytotoxic reactivity. These findings demonstrate the reversal of a central inhibition of immune cell activity. The explanations offered for this phenomenon included change in surface characteristics of the immune cells during in vitro incubation, and the possible need for an adherent helper cell.
SPECIFIC ADHERENCE OF IN VITRO DIFFERENTIATED LYMPHOCYTES TO TARGET CELLS
Authors: Hollander Nurit , Ginsburg Haim
Published: June 2004

Blast cells which were derived from rat lymphocytes by stimulation with phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM) transformed within 2–3 days into a new type of lymphocytes when plated without mitogen on embryo fibroblast monolayers. These lymphocytes were termed secondary lyrophocytes. Upon addition of PWM to PWM-secondary lymphocytes a marked adherence to fibroblast monolayers was observed. The degree of adherence was estimated (a) by direct count of the lymphocytes in the medium and in the trypsinized fibroblast fraction, and (b) by using 51Cr-labeled lymphocytes. The adherence process required incubation at 37°C. The process started immediately after the addition of PWM and reached a plateau at 6 hr. At this time more than 80% of the lymphocytes adhered. In the absence of PWM only 12% of the lymphocytes were found in the fibroblast fraction. Unlike PWM-lymphocytes. Con A-lymphocytes, PHA-lymphocytes, and ordinary lymphocytes taken directly from the rat lymph nodes adhered only slightly more in the presence of PWM (10–20% adherence of ordinary lymphocytes) than in its absence (8% adherence). The adherence of the secondary lymphocytes and the ordinary lymphocytes was also studied in the presence of Con A and PHA. These mitogens induced high rate of adherence and they did not demonstrate specificity in their action. The adherence was accompanied by transformation of the lymphocytes to blast cells endowed with target-cell lytic ability. This transformation occurred mostly in the adhering fraction of the lymphocyte population. The results support the notion that target-cell recognition and destruction in cellular immunity involve contact between the cells.
LYSOSOMES IN RAT THORACIC DUCT LYMPHOCYTES
Authors: Bowers William E.
Published: June 2004

10 acid hydrolases known to be lysosomal in other tissues were detected in rat thoracic duct lymphocytes (TDL). Except for cathepsin D, all these enzymes occurred in lower levels in TDL than in rat spleen.

Fractionation by means of differential centrifugation revealed two types of distribution patterns. Most of the total cathepsin D activity appeared in a high-speed supernatant (S), whereas the other acid hydrolases associated mainly with a high-speed pellet (P). Further studies by isopycnic centrifugation in a sucrose density gradient showed that all the enzymes, including a small portion of cathepsin D, sedimented around a modal density of 1.18. In contrast, most cathepsin D activity was recovered in a soluble, unsedimentable form. These results suggest the presence of two populations of lysosomes. Because the possibility could be excluded that other cell types contaminated the lymphocyte preparations, it is concluded that both lysosomal populations arise from TDL.
RAPID VIRAL INDUCTION OF MURINE LYMPHOMAS IN THE GRAFT-VERSUS-HOST REACTION
Authors: Cornelius Eugene A.
Published: June 2004

When weanling (SJL/J x C57BL/1)F1 hybrid mice were given five weekly-injections of small doses of viable SJL/J spleen cells, so as to induce a graft-versus-host reaction (GVHR), reticulum cell sarcomas were induced in all of the host mice by the 40th day after the first cell injection. Such tumors, on transplantation, were accepted by syngeneic (SJL/J x C57BL/1)F1 and C57BL/1 hosts, but not by SJL/J or NZB mice. Cell-free extracts of SJL/J spleens injected into similar hybrids resulted in identical tumors in all hosts within the same period; the transplantation characteristics were also similar. Normal (SJL/J x C57BL/1)F1 hybrids as well as similar hybrids injected with SJL/J liver or syngeneic F1 spleen cells did not develop tumors.

Cell-free preparations of eight tumors induced in F1's by viable SLJ/J spleen cells were injected into newborn (C57BL/1 x A)F1 and C57BL/1 mice: tumors were induced, with seven of eight tumor preparations, with a latent period of 33–49 days. Such tumors were lymphosarcomas, and, in the case of (C57BL/1 x A)F1 hosts, further transplantation revealed that they were antigenically C57BL/1 tumors.

These experiments provide conclusive evidence for a viral etiology of GVHR-induced tumors. Furthermore, tumor induction in the GVHR does not appear to depend specifically on an immunological mechanism but is most probably due to release or activation of a sufficient quantity of oncogenic virus within a certain time period in a highly susceptible host. Comparison with radiation induction of viral leukemia in mice revealed similarities in regard to optimal host age and the spacing of administration of the tumor-inducing agent.

SJL/J mice carry a type C virus which causes a high incidence of spontaneous Hodgkin-like tumors by 1 yr of age; C57BL/1 mice do not develop lymphomas spontaneously but carry a latent leukemogenic virus. Their hybrid also has a low incidence of spontaneous lymphomas. Based on the results of these and previous experiments, the viruses of these strains of mice appear to be highly synergistic in tumor induction in the GVHR. The SJL/J virus is a powerful oncogenic agent. The C57BL/1 virus may be a helper virus to the SJL/J, but is a more powerful determinant of the antigenic composition of the induced tumors. This suggests that the virus of C57BL/1 mice, when activated, is capable of controlling the C57BL/1 genome. Because of the ease and rapidity of viral tumor induction, the SJL/J and C57BL/1 strains of mice, with their F1 hybrid, should be useful for further study of the mechanisms controlling induction of such tumors.
DEPRESSED CELL-MEDIATED IMMUNITY IN PATIENTS WITH PRIMARY INTRACRANIAL TUMORS
Authors: Brooks William H. , Netsky Martin G. , Normansell David E. , Horwitz David A.
Published: June 2004

Tumor immunity in patients with primary intracranial tumors was assessed in relation to the general status of host immunocompetence. Lymphocyte sensitization to tumor-specific membrane antigens was demonstrated by the proliferative response of lymphocytes in the presence of autochthonous tumor cells. Paradoxically, one-half of the patients could not be sensitized to a primary antigen, dinitrochlorobenzene; existing delayed hypersensitivity was also depressed, as measured by skin tests and lymphocyte transformation in response to common antigens.

A heat-stable factor in patients' sera blocked cell-mediated tumor immunity. In addition, these "enhancing" sera consistently suppressed the blastogenic response of autologous and homologous lymphocytes to phytohemagglutinin and to membrane antigens on allogeneic cells in the one-way mixed lymphocyte culture. When patients' leukocytes were washed and autologous plasma replaced with normal plasma, reactivity in the mixed lymphocyte culture increased to normal values.

In vitro immunosuppressive activity in patients' plasma or sera correlated with depressed delayed hypersensitivity. After removal of the tumor, suppressor activity disappeared. IgG fractions of patient sera contained strong immunosuppressive activity. These data suggest that the suppressor factor may be an isoantibody elicited by the tumor that also binds to receptors on the lymphocyte membrane. In addition to specifically blocking cell-mediated tumor immunity, enhancing sera may broadly depress host immunocompetence.
INDUCTION OF TOLERANCE TO SHEEP RED BLOOD CELLS
Authors: Anderson Traute-Heidi , Roethle Joan , Auerbach Robert
Published: June 2004

Adult mice injected with a sheep red blood cell hemolysate supernatant fraction were found to have a severely reduced responsiveness to subsequent immunization with sheep red blood cells. The induced unresponsiveness was found to be specific, as tested by reciprocal experiments involving horse and sheep erythrocyte preparations. The tolerogenic material did not appear to be immunogenic.
PURIFIED PROTEIN DERIVATIVE OF TUBERCULIN INDUCES IMMUNOGLOBULIN PRODUCTION IN NORMAL MOUSE SPLEEN CELLS
Authors: Nilsson Bengt S. , Sultzer Barnet M. , Bullock Wesley W.
Published: June 2004

Purified protein derivative (PPD) tuberculin induced immunoglobulin production in cultures of nonimmune mouse spleen cells, as measured by plaque-forming cells (PFC) against sheep erythrocytes (SRBC), horse erythrocytes, and 4-hydroxy-3,5-dinitrophenacetyl-SRBC. The increase started between 15 and 20 h of culture and reached a peak at 48–72 h. Higher PPD concentrations resulted in earlier peak responses than low concentrations. The Ig produced was mainly 19S and of very low avidity. The response elicited by PPD was of the same type as that caused by lipopolysaccharide of bacterial origin. Mitomycin treatment of cells before culture did not change the numbers of PFC/106 recovered cells but the cell recovery was considerably lower.

Also injection of PPD in vivo resulted in increased numbers of PFC. On the basis of these results it is suggested that PPD nonspecifically activates a majority of the B cell population to proliferation and immunoglobulin synthesis.
EPSTEIN-BARR VIRUS
Authors: Shope Thomas , Miller George
Published: June 2004

Epstein-Barr virus (EBV)-transformed autologous lymphoblasts were repeatedly inoculated into three squirrel monkeys. Each animal developed the heterophile antibodies of infectious mononucleosis and EBV-specific antibodies. After serologic responses had disappeared or markedly declined, the animals were challenged with either whole cells, cell filtrate, or cell ghosts. Animals challenged with living cells and cell ghosts developed agglutinin responses; the recipient of filtrate did not. The results suggest that EBV induces the appearance of the infectious mononucleosis heterophile antigen on the transformed cell membrane.
ESCAPE FROM ISOANTISERUM INHIBITION OF LYMPHOCYTE-MEDIATED CYTOTOXICITY
Authors: Faanes R. B. , Choi Y. S. , Good R. A.
Published: June 2004

Isoantiserum (IS) inhibition of lymphocyte-mediated cytotoxicity (LMC) was studied using an in vitro 51Cr release assay system. In the early phase of incubation, LMC was competitively inhibited by IS. However, as the incubation continued, LMC irreversibly overcame IS inhibition (the "escape" phenomenon). Addition of fresh antiserum did not alter the course of the escape. Low-temperature incubation of isoantibody-coated target cells delayed the onset of the escape.

We have excluded the possibility that the escape phenomenon is induced by complement or by LMC mediated by antigen-antibody complex. It is hypothesized that antibody directed toward an actively metabolizing target cell induces an alteration in the cell membrane that alters further interaction with the antibody. However, sensitivity to lymphocyte cytotoxicity is maintained.
STUDIES ON GONOCOCCUS INFECTION
Authors: Buchanan Thomas M. , Gotschlich Emil C.
Published: June 2004

Comparable numbers of types 1, 2, 3, and 4 gonococci were placed on the intact chorioallantoic membrane of 236, 10-day old chick embryos. Types 1 and 2 organisms produced infection and could be cultured from chorioallantoic fluid 2 days later significantly more often (69%) than types 3 and 4 organisms (12%, P < 0.001). This confirms in an animal model the same correlation between colony types and infectivity observed in human volunteers and suggests that types 1 and 2 gonococci possess a fundamental virulence characteristic which is absent from types 3 and 4 organisms. Gonococcal infection of the chick embryo chorioallantoic cavity remains a useful model somewhat analogous to localized gonococcal infection in man.
SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE
Authors: Tigelaar Robert E. , Asofsky Richard
Published: June 2004

Spleen cells from normal adult mice were injected into lethally irradiated adult syngeneic recipients. 24 h later, cell suspensions were prepared from the recipients' spleens or peripheral lymph nodes and tested either alone or combined for their capacity to elicit graft-versus-host (GVH) reactions in neonatal F1 recipients, using the Simonsen spleen weight assay.

Either the lymph node-seeking subpopulation or the spleen-seeking subpopulation alone was markedly deficient in its ability to provide a GVH reaction when compared with the normal population from which it was derived. However, an appropriate mixture of the two had a reactivity characteristic of the parent population. Both subpopulations were sensitive to treatment with anti-θ antibody and complement in vitro.

These results provide a convincing demonstration of the functional heterogeneity within the pool of thymus-derived cells present in a single normal lymphoid tissue. They strongly suggest that the normal expression of GVH reactivity of such a tissue involves an interaction among distinct subpopulations of thymus-derived cells.
SEPARATION OF HUMAN LYMPHOID CELLS INTO G1, S, AND G2 CELL CYCLE POPULATIONS BY USE OF A VELOCITY SEDIMENTATION TECHNIQUE
Authors: Everson Lloyd K. , Buell Donald N. , Rogentine G. Nicholas
Published: June 2004

Human lymphoid tissue culture cells can be separated according to cell size and corresponding cell cycle phase with a velocity sedimentation centrifugation method employing a continuous 5–20% wt/wt Ficoll gradient. A 7-fold increase in streaming limit was achieved by placing a buffer zone of isosmolar 5% Ficoll on top of the gradient before application of the cell load.

The various pooled populations of cells from upper, middle, and lower areas of the gradient were characterized using autoradiographic, TCA-precipitable 3H]thymidine incorporation, and Fuelgen microspectrophotometric methods. The upper range of the gradient contains cells in the G1 cell cycle phase; the lower range, cells in the G2 phase; cells found in the middle of the gradient belong largely to the S phase of the cell cycle.

These gradient-separated cell pools contained relatively little contamination with cells from other phases of the cell cycle and, when explanted from the gradient into fresh growth media, showed growth patterns characteristic of synchronized cell populations. This system of cell separation provides a useful tool for investigating the relationship of the cell cycle to surface membrane and metabolic characteristics in human lymphoid cell culture systems.
HETEROGENEITY OF THE EFFECTOR CELLS IN THE CYTOTOXIC REACTION AGAINST ALLOGENEIC LYMPHOMA CELLS
Authors: Forman James , Britton Sven
Published: June 2004

The cytotoxic effect of spleen cells from H-2 allogeneic mice was tested in vitro against an A strain leukemia (YAC) labeled with [125I]iododeoxyuridine. After the mice were primed with tumor cells, significant and specific H-2 immunity was detected on day 3 and peak cytotoxicity was observed between 7 and 14 days after priming. Two effector cells appear to be involved in the host response, because spleens taken from mice soon after priming were not sensitive to antitheta sera and complement while those taken during the peak stages of the response showed a marked reduction in cytotoxicity after treatment. Macrophages were not involved, since removal of these cells by the carbonyl iron method did not result in any reduction in cytotoxicity. Immune serum that was capable of inducing cell-mediated cytotoxicity in normal spleen cell populations also augmented cytotoxicity of spleen cells taken from mice primed 3 days previously. However, when spleen cells were taken from mice during the peak phase of the immune response, the same serum at the same dilutions inhibited the preexisting cytotoxicity. A difference was also detected in the killing efficiencies between early and late immune cells.
THE RELATIONSHIP OF GLYCINE-RICH ß-GLYCOPROTEIN TO FACTOR B IN THE PROPERDIN SYSTEM AND TO THE COBRA FACTOR-BINDING PROTEIN OF HUMAN SERUM
Authors: Alper Chester A. , Goodkofsky Ira , Lepow Irwin H.
Published: June 2004

Factor B activity of the properdin system was found to be identical with purified glycine-rich ß-glycoprotein (GBG) but was distinct from the normal human serum protein capable of forming a C3-inactivating complex with a protein from cobra venom (CoF). Factor B activity coincided with electrophoretically separated GBG genetic variants, whereas the CoF-binding protein did not. GBGase destroyed factor B as it cleaved GBG but did not destroy the C3-inactivating activity of the CoF-binding protein. During incubation of serum with CoF, GBG did not change in molecular size, nor was there any coincidence in the immunoelectrophoretic mobilities of CoF and GBG. It was not possible to precipitate labeled CoF incubated with serum by anti-GBG, nor labeled GBG from serum incubated with CoF by anti-CoF.

The CoF-binding capacity of serum was 2 mg/100 ml or less or under 6.5% of the serum concentration of GBG. When labeled CoF was added to serum below the binding capacity, complete complexation of the CoF was demonstrated, whereas CoF was largely uncomplexed when CoF was added in amounts equimolar to GBG.
A PEROXIDASE-MEDIATED, STREPTOCOCCUS MITIS-DEPENDENT ANTIMICROBIAL SYSTEM IN SALIVA
Authors: Hamon Charles B. , Klebanoff Seymour J.
Published: June 2004

H2O2 formation by Streptococcus mitis was measured by the catalase-dependent conversion of [14C]formate to 14CO2 ; it was optimal at pH 6.0–6.5 and required glucose. The H2O2 formed by S. mitis could be employed as a component of an antimicrobial system that also included lactoperoxidase (LPO) and either iodide or thiocyanate ions in the concentrations present in saliva. The antimicrobial effect of the LPO-iodide-S. mitis system was measured by the decrease in the viable cell count of the target organisms (Escherichia coli, Staphylococcus aureus, Candida tropicalis). The antimicrobial effect of the LPO-thiocyanate-S. mitis system was measured by the decrease in the rate of growth or the rate of uptake of [14C]valine by the target organisms (E. coli, S. aureus). Mixed or parotid saliva could replace LPO and thiocyanate ions in the S. mitis-dependent inhibition of bacterial growth and valine uptake. The presence in saliva of a peroxidase-mediated, antimicrobial system dependent on microbial metabolism for H2O2 and its role as a natural host defense mechanism are considered.
2,4-DINITROPHENYL RECEPTORS ON MOUSE THYMUS AND SPLEEN CELLS
Authors: Lawrence David A. , Spiegelberg Hans L. , Weigle William O.
Published: June 2004

A higher percentage of specific antigen-binding cells can be detected not only in normal CBA/J mouse spleen cell preparations (0.99%), but also in the normal thymus cell preparations (0.15%) with the use of [125I]2,4-dinitrophenyl-human IgG (DNP-HGG) as compared with most other antigens employed under similar conditions. The receptors on these cells are mainly specific for the DNP group as shown by the inhibition studies with DNP-lysine and the other DNP conjugates. In addition, it was shown by the inhibition studies with DNP-lysine that the thymus cells seem to have a lower avidity for DNP than the spleen cells. Preincubation of cell suspensions with antisera to immunoglobulins showed that the DNP-HGG antigen-binding cells in the thymus are inhibited predominantly with anti-µ-chain serum and the spleen cells with both anti-µ-chain and anti-γ-chain sera; both cell populations were also significantly inhibited with the antisera to κ-chains and Fab fragments. These data indicate that the nature of the receptor on the T cell differs from that on the majority of spleen cells.
CONSEQUENT INTRAFAMILIAL IMMUNIZATION FOR DL-A HAPLOTYPING IN CANINES
Authors: van der Does J. A. , van Rood J. J. , Walker W. S. , Epstein R. B.
Published: June 2004

A procedure of intrafamilial immunization is described for production of antisera recognizing DL-A haplotypes. In a colony consisting of 1 sire, 6 bitches, and 67 offspring all haplotypes could be accurately allocated. In the colony the observed reaction frequencies of the antisera are in agreement with mendelian codominant inheritance. Mixed lymphocyte culture tests confirmed the accuracy of the serologic typing and the presence of homozygous individuals within the colony. Further evidence is presented supporting the presence of two or more subloci within the DL-A system. Colonies of canines such as the one described should provide a sensitive system for evaluating interaction between serologic DL-A typing, MLC reactivity, and immune response genetics in a nonrodent species which is not highly inbred.
PRODUCTION OF TL ANTIBODY BY MICE IMMUNIZED WITH TL- CELL POPULATIONS
Authors: Komuro Katsutoshi , Boyse Edward A. , Old Lloyd J.
Published: June 2004

TL- mice make TL antibody when immunized with spleen or bone marrow cells from TL+ donors, despite the fact that these cells do not express TL antigen. This has been shown to depend on maturation of TL- precursors, contained in the inoculum, into TL+ cells under influence of the recipient's thymus; the differentiated TL+ cells then evoke production of TL antibody.
PROLIFERATION OF DONOR MARROW AND THYMUS CELLS IN THE MYELOID AND LYMPHOID ORGANS OF IRRADIATED SYNGENEIC HOST MICE
Authors: Takada Akikazu , Takada Yumiko
Published: June 2004

CBA/HT6T6 bone marrow cells (1 x 107) or CBA/H bone marrow cells (1 x 107) plus CBA/HT6T6 thymus cells (5 x 107) were injected intravenously into lethally (800 R) irradiated CBA/H mice. Chromosome analyses of dividing cells in the host lymphoid and myeloid organs were performed at intervals after irradiation.

Donor marrow cells settled and proliferated in the host bone marrow, spleen, and lymph nodes soon after injection, but donor marrow cells did not proliferate in the host thymus until day 10; then host-type cells were quickly replaced by donor-type cells in the thymus by day 20. On the other hand, donor thymus cells settled and proliferated in the host thymus and lymph nodes soon after injection but they gradually disappeared from these organs. On day 20, a few donor-type dividing cells (of thymus origin) were found in the host lymphoid and myeloid organs.
STIMULATION OF IGG ANTIBODY RESPONSE IN VITRO BY T CELL-REPLACING FACTOR
Authors: Schimpl A. , Wecker E.
Published: June 2004

A soluble factor (TRF) produced by mixtures of allogeneic mouse spleen, lymph node, and thymus cells functionally replaces T cells in a primary IgM antibody response to sheep blood cells in vitro. It is now shown that TRF can also reconstitute an IgG antibody response in T cell-deprived spleen cultures derived from preimmunized mice. The optimal time of addition and the amount of TRF required differ between primary and secondary in vitro systems.
CELL-MEDIATED IMMUNITY AND BLOCKING SERUM ACTIVITY TO TOLERATED ALLOGRAFTS IN RATS
Authors: Bansal S. C. , Hellström K. E. , Hellström I. , Sjögren H. O.
Published: June 2004

W/Fu rats were neonatally inoculated with bone marrow cells from B/N rats and vice versa. Of the inoculated rats, some were capable of accepting a foreign (B/N or W/Fu) skin graft over the period of observation (i.e. for more than 100 days), while other rats rejected their skin grafts as early as control animals (within 8–12 days) or after a prolonged period of acceptance (20–96 days).

Using a microcytotoxicity test, it could be shown that both those rats that rapidly rejected skin grafts and those that kept their grafts during the observation period had lymphocytes capable of destroying cultivated allogeneic cells from the respective strains with whose cells the rats had been inoculated as newborns. The degree of lymphocyte reactivity decreased upon time, so that 4 of 13 rats that had carried "tolerated" skin grafts over more than 84 days had lymphocytes which were nonreactive in the highest dose tested, and the degree of reactivity in the other 9 rats was less than seen early after tolerance induction.

Rats that were capable of accepting skin grafts over prolonged periods of time had sera that could specifically block lymphocyte-mediated cytotoxicity, while sera from rats that had rejected their grafts did not block. Sera from rats that rejected their skin grafts after 20–96 days lost the blocking activity 3–10 days before rejection.