bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective deficiency of a T cell subpopulation in active atopic dermatitis.
Authors: Schuster D L , Bongiovanni B A , Pierson D L , Barbaro J F , Wong D T , Levinson A I
Published: December 2022

The T cell subpopulation bearing a receptor for the Fc fragment of IgM (T mu) or the Fc fragment of IgG (T gamma) were studied in 12 patients with active atopic dermatitis (AD) and elevated IgE (5678 I.U./ml +/- 1382) and compared with a control group with normal IgE (33 +/- 17). Values for the total lymphocytes and for absolute and relative numbers of total T and T mu cells were comparable in both groups. However, AD patients had markedly reduced relative T gamma levels, 1.8% +/- 0.4%, compared with normals, 10.5% +/- 0.7% (p less than 0.001). The patients also had reduced absolute T gamma levels, 29 +/- 7, compared with 181 +/- 36 (p less than 0.0005). This abnormality was not indicative of allergic disease in general, nor did it appear to be caused directly by serum factors. The T gamma cell deficit did reflect disease activity and correlated inversely with the levels of serum IgE in the AD patients. Thus, patients with active AD and elevated IgE have a selective reduction in circulating T gamma cells.
Characterization of natural cytotoxicity in vitro in a spontaneous rat tumor model.
Authors: Zöller M , Matzku S
Published: December 2022

Spontaneous rat tumor cells were tested in a 12-hr Cr-release assay for susceptibility or resistance to cytolysis by lymphoid effector cells from untreated rats. Most target cells were intermediate to highly susceptible (up to 85% lysis at an effector-to-target ratio of 50:1), but we observed nonsusceptible target cells, too. Cold target inhibition experiments confirmed the susceptibility classifications obtained in the direct assay. The functional properties of effector cells paralleled closely the known properties of natural killer cells. The NK responsiveness of various rat strains did not coincide with the incidence of spontaneous tumors.
The transient appearance of degenerate antibody early in the course of the immune response.
Authors: Kan E A , Siskind G W
Published: December 2022

The appearance of degenerate antibody-secreting cells early in the course of the immune response was demonstrated. Mice immunized with SRBC had anti-SRBC plaques that were as much as 95% inhibitable by DNP-Ova or DNP-KLH, and mice immunized with DNP-KLH had anti-DNP plaques that were as much as 90% inhibitable by Fl-BGG. In addition, mice immunized with BRBC produced plaques detectable on TNP-SRBC. The data suggest that, early after antigen injection, antibody is produced that can react with both the immunizing antigen and with structurally unrelated antigenic determinants. The incidence of such degenerate antibody-secreting cells is maximal at 3 days after antigen injection and decreases thereafter. It is probable that the degenerate antibody is of very low affinity for the immunizing antigen.
Linkage of severity of experimental allergic encephalomyelitis to the rat major histocompatibility locus.
Authors: Moore M J , Singer D E , Williams R M
Published: December 2022

The incidence of EAE is determined by Ir-EAE, a gene linked to the rat MHC. EAE severity can be assessed by quantitative clinical and pathologic measures. Using these measures, one can say that disease severity in LBNF1 is approximately one-tenth that in Lewis. Analysis of LBNF2, LBC, BNBC, and parental Lewis strain reveals that severity is primarily a function of dose of Lewis MHC alleles. Non-MHC genes have a small but discernable effect.
Mapping of the X-linked immune deficiency mutation (xid) of CBA/N mice.
Authors: Berning A K , Eicher E M , Paul W E , Scher I
Published: December 2022

CBA/N mice carry a recessive mutation at the X-linked immune deficiency (xid) locus that precludes their response to certain thymus-independent (TI) antigens. We have determined that xid is situated on the X-chromosome between the genes Ta (tabby) and Hyp (hypophosphatemia), genetic distances being Ta-6.6 +/- 1.8-xid-12.2 +/- 2.3-Hyp.
A new class of inhibitors of lymphocyte mitogenesis: agents that induce erythroid differentiation in Friend leukemia cells.
Authors: Novogrodsky A , Rubin A L , Stenzel K H
Published: December 2022

Addition of the polar organic compounds, dimethylsulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, and butyric acid, to human lymphocyte cultures stimulated with the tumor-promoting agent, phorbol myristate acetate, results in greater than 90% inhibition of lymphocyte proliferation. Inhibition is achieved at concentrations of the organic compounds reported to be optimal for induction of erythroid differentiation in Friend leukemia cells. Butyric acid is the most potent compound tested. Compounds that are structurally related to butyric acid, but that do not induce erythroid differentiation, do not inhibit lymphocyte mitogenesis. Lymphocyte responses to other mitogens are also suppressed by the polar organic compounds, although higher concentrations are required. These agents are much less inhibitory when added 24 hr after initiation of the cultures, indicating that they may affect an early phase of lymphocyte activation. Compounds that induce erythroid differentiation in Friend leukemia cells constitute a new class of inhibitors of lymphocyte mitogenesis.
Inductive requirements for the generation of virus-specific T lymphocytes. II. Poxvirus and H-2 antigens associate without cellular or virus-directed protein synthesis, and remain immunogenic in cell membrane fragments.
Authors: Hapel A J , Bablanian R , Cole G A
Published: December 2022

The nature of the interaction between vaccinia virus (VAC) and fibroblastic cells that renders the latter capable of being recognized by virus-specific, H-2 identical murine T lymphocytes has been studied. L cells exposed for 10 min to VAC rendered noninfectious by exposure to ultraviolet light became susceptible targets for cytotoxic T lymphocytes (CTL) without the synthesis of new viral proteins. Susceptibility was retained even if cellular protein synthesis was irreversibly inhibited with pactamycin before virus exposure. Immobilization of cell-surface membranes by glutaraldehyde fixation before (but not after) exposure to virus severely impaired the formation of the "virus + self" complex that in vitro stimulated secondary CTL responses by H-2 identical virus-primed memory cells even though virus attachment to fixed cells were unaffected. This stimulatory complex, once formed, was maintained in membrane fragments prepared from cells previously exposed to VAC. These findings indicate that VAC-specific CTL or their immediate precursors can recognize only those viral envelope antigens that become membrane integrated and that this event requires neither host cell-specific nor virus-specific protein synthesis.
Minimal molecular requirements for reactivity of tumor cells with T cells.
Authors: Hale A H , Lyles D S , Paulus L K , Ruebush M J
Published: December 2022

We have investigated the minimal molecular requirements for T cell recognition of a previously described myeloma tumor (MOPC-315-EL), which reversibly alters its reactivity with T cells. Enucleation of MOPC-315 cells, either sensitive or resistant to reaction with T cells, did not alter the ability of the resulting cytoplasts to elicit or serve as targets for anti-H-2 or anti-Sendai viral cytotoxic T lymphocytes (CTL), despite the fact that there were no detectable differences in serologically defined H-2 or viral antigens on their surface. Likewise, when plasma membranes isolated from sensitive or resistant cells were tested for their ability to elicit anti-H-2 CTL, they retained the phenotype of the cells from which they were isolated. However, solubilized and partially purified H-2 antigens from both sensitive and resistant cells were able to elicit H-2-restricted anti-Sendai virus CTL when incorporated into liposomes with purified viral glycoproteins, and anti-H-2 CTL when incorporated alone into liposomes. These results suggest that a cellular surface component(s) exists that is probably not an H-2K or H-2D gene product and is responsible for the reversible variation in the reactivity of the tumor cells with T cells.
Mitogen-induced plasma cell differentiation in patients with multiple sclerosis.
Authors: Levitt D , Griffin N B , Egan M L
Published: December 2022

Cellular interactions involved in mitogen-stimulated plasma cell differentiation were investigated in eight patients with severe but stable multiple sclerosis (MS). No significant differences were detected between normals and MS patients with regard to percent of B lymphocytes and T lymphocytes in peripheral blood. Autologous and allogeneic combinations of normal and MS B and T cells were stimulated with pokeweed mitogen (PWM) and E. coli lipopolysaccharide (LPS), and plasma cell differentiation was monitored after 7 days in culture. T lymphocytes from patients with MS induced 2- to 4-fold increases in plasma cell development when combined with normal B cell fractions. Allogeneic combinations on normal B and T cells did not provide enhanced plasma cell generation. B lymphocytes from MS patients exhibited poor responses to both PWM and LPS when cultured with their own or normal T cells. Such B cell fractions did not differ from normals with regard to percent monocytes or surface Ig+ B lymphocytes initially contained in these cell populations. We conclude that T cells from MS patients are able to provide excessive help for normal B cell differentiation due either to increased T helper activity or deficient T suppressor activity. B cell differentiation may be diminished in MS patients as a result of a deficiency of a population of B cells in blood that are able to be stimulated by polyclonal B cell activators.
Rat alveolar macrophages are susceptible to activation by free and liposome-encapsulated lymphokines.
Authors: Sone S , Poste G , Fidler I J
Published: December 2022

Alveolar macrophages (AM) obtained from F344 rats were rendered tumoricidal by incubation in vitro with cellfree culture supernatant fluids rich in macrophage-activating factor (MAF) activity harvested from mitogen-stimulated F344 rat lymphocytes. AM activated by this procedure destroyed syngeneic, allogeneic, and xenogeneic tumor cells but were not cytotoxic for nonneoplastic cells. MAF was encapsulated in multilamellar lipid vesicles (liposomes) and its ability to render AM tumoricidal was compared with that of free (unencapsulated) MAF. Liposome-encapsulated MAF rendered AM cytotoxic at concentrations up to 16,000 times lower than free MAF. These data demonstrate that AM can respond in vitro to lymphokines and that MAF encapsulated within liposomes is far more efficient in rendering AM tumoridical than free MAF.
Life-span and size of the trans-membrane channel formed by large doses of complement.
Authors: Ramm L E , Mayer M M
Published: December 2022

To evaluate the life-span and size of trans-membrane channels in complement (C) treated membranes, resealed erythrocyte ghosts containing trapped native protein markers, as well as residual hemoglobin, were treated with anti-Forssman antibody and large doses of guinea pig C. Ovalbumin and hemoglobin were released slowly through the channels so produced, whereas human serum albumin was not. Release of hemoglobin was not blocked by extracellular bovine serum albumin. Release of hemoglobin continued for at least 72 hr at 4 degrees C. Semi-logarithmic plots of ovalbumin or hemoglobin release showed gradual diminution of the rate constant, which indicates slow loss of channels during the experimental period. These experiments demonstrate that the channels produced in erythrocyte ghost membranes by large C doses have a long, although finite, life-span. Their effective diameter is al least 55 A on the basis of ovalbumin and hemoglobin release, and not more than 150 A, since serum albumin was not released. However, an upper limit of 100 A would be more reasonable in light of electronmicroscopic observations by others. These results are compatible with the doughnut model.
Induction of cytotoxic T lymphocytes against herpes simplex virus type i: role of accessory cells and amplifying factor.
Authors: Rouse B T , Lawman M J
Published: December 2022

Spleen cells from mice primed with herpes simplex virus type 1 (HSV-1) could be induced to differentiate into cytotoxic T lymphocytes (CTL) by in vitro culture with infectious HSV-1 but not by heat-inactivated virus. Induction of CTL failed to occur if the spleen cells were depleted of adherent cells by passage over columns of nylon wool before culture with virus. The CTL response could be restored by adding normal syngeneic peritoneal cells (PC) or L cell fibroblasts but not by allogeneic PC or BALB/c 3T3 fibroblasts. Thus, the induction of HSV-1-specific CTL was H-2 restricted. The response of HSV-1-stimulated nylon wool-depleted spleen cells could also be restored by adding amplifying factor (AF) produced in 24 hr mixed lymphocyte cultures. The addition of AF to nondepleted spleen cells also permitted the generation of CTL with heat-inactivated HSV-1 as a viral stimulant. Our results indicated that induction of a HSV-1 CTL response requires two signals, one provided by virus and a second, presumably nonspecific, by helper T cells. It was suggested that only the helper cells require H-2 restriction and need to be presented virus in the context of a macrophage.
Effect of neonatal injection of anti-mu antibodies on immunity to schistosomes (S. mansoni) in the rat.
Authors: Bazin H , Capron A , Capron M , Joseph M , Dessaint J P , Pauwels R
Published: December 2022

The effect of neonatally initiated injections of anti-mu serum on immunity to reinfection with Schistosoma mansoni in the rat was investigated in vitro and in vivo. Anti-mu treatment resulting in a profound depression of immunoglobulin synthesis dramatically decreased immunity to reinfection assessed by worm recovery technique. Complement-dependent antibody, IgG2a antibody-eosinophil-mediated and IgE-macrophage cytotoxicity reactions were in parallel markedly reduced. These results show the prominent role played by antibody-dependent mechanisms in immunity to schistosomes in the rat.
A comparative investigation of the generation of specific T cell-helper function induced by Streptococcus mutans in monkeys and mice.
Authors: Lamb J R , Kontiainen S , Lehner T
Published: December 2022

Antigen-specific helper cells were induced in vitro in monkeys and mice by using an antigen preparation from Streptococcus mutans. These helper cells were T cells on the basis of their sensitivity to anti-Thy. I and complement, and were not retained on nylon wool. Upon further in vitro culture the helper cells release mediators of help, "helper factor" in the supernatant. The release of helper factor as well as its augmentation of the immune response was antigen specific. Monkey and murine helper factors were similar in their induction, function, and specificity.
Activation of human B lymphocytes. XV. Spontaneously occurring and mitogen-induced indirect anti-sheep red blood cell plaque-forming cells in normal human peripheral blood.
Authors: Fauci A S , Whalen G , Burch C
Published: December 2022

A system for the development of indirect (IgG, IgA, and IgM) anti-SRBC plaque-forming cells (PFC) after polyclonal stimulation of human peripheral blood lymphocytes with pokeweed mitogen (PWM) is described. Rabbit anti-human polyvalent Ig or Ig class-specific antisera were employed. Most of the indirect PFC were IgG with less being IgM and IgA. The finding of significantly more indirect IgM PFC than direct PFC suggests that many IgM PFC are producing low efficiency hemolysin that requires an anti-globulin to produce lysis. The system is T cell dependent and cultures require selected batches of supplemented fetal calf serum that preferentially yield indirect (1527 +/- 243 PFC/10(6) lymphocytes) as opposed to direct (36 +/- 11 PFC/10(6) lymphocytes) PFC. Batches of human AB sera that were previously chosen to yield optimal direct PFC (approximately 200 to 300 PFC/10(6) lymphocytes) did not yield indirect PFC. Hence, depending on culture conditions, polyclonal stimulation of human lymphocytes can yield antigen-specific direct and indirect hemolytic PFC.
Glucocorticoids and lymphocytes. I. Increased glucocorticoid receptor levels in antigen-stimulated lymphocytes.
Authors: Crabtree G R , Munck A , Smith K A
Published: December 2022

Recently a 2- to 3-fold increase in the number of glucocorticoid receptors in human peripheral lymphocytes has been noted after in vitro mitogen stimulation. Here, we extend these observations to in vivo immunization. After unilateral immunization of adrenalectomized male rats, a 50% increase in glucocorticoid receptor sites per cell, determined by binding of dexamethasone, was observed in cell suspensions of homolateral lymph nodes over those from the contralateral nonimmunized side of the same animal. The association constant for dexamethasone was similar in both groups, as was the stereospecificity for various steroids, the time course of cytoplasmic and nuclear association, and cytoplasmic-to-nuclear translocation. Despite a 50% increase in the number of glucocorticoid receptor sites per cell, the cells from the homolateral and controlateral lymph nodes were equally sensitive to the inhibitory effects of dexamethasone, as determined by measurements of the incorporation of radiolabeled precursors of protein, RNA, and DNA, or measurements of in vitro cell survival.
Specificity of alloreactive T lymphocytes that adhere to lung stage schistosomula of Schistosoma mansoni.
Authors: Brown A P , Burakoff S J , Sher A
Published: December 2022

Alloreactive T lymphocytes generated against MHC antigens have previously been shown to adhere to lung stage schistosomula of S. mansoni because of the host MHC products known to be present on the surface of the parasites. In experiments reported here, the cells in this adherent population were shown to consist of Ly-2 positive, Thy-1 positive lymphocytes and to react specifically with products of the K and D but not the I region of the MHC. These results strengthen previous findings suggesting that the adherent lymphocytes are CTL.
Ecto-5'-nucleotidase activity in lymphoblastoid cell lines derived from heterozygotes for congenital X-linked agammaglobulinemia.
Authors: Thompson L F , Boss G R , Spiegelberg H L , Bianchino A , Seegmiller J E
Published: December 2022

Lymphoblastoid cell lines were established from female relatives of patients with congenital X-linked-agammaglobulinemia by Epstein-Barr virus transformation of their peripheral B lymphocytes. Cell lines derived from presumed carriers were characterized by low ecto-5'-nucleotidase activity and a reduced percentage of surface immunoglobulin-bearing cells. Measurement of ecto-5'-nucleotidase activity in newly established lymphoblastoid cell lines may provide a means for the identification of heterozygotes for congenital X-linked agammaglobulinemia.
EBV-transformation of surface IgA-positive human lymphocytes.
Authors: Steinitz M , Klein G
Published: December 2022

Surface IgA-positive human lymphocytes were selected, separated, and immortalized with Epstein-Barr virus (EBV). Selection was carried out by rosetting the cells with ox erythrocytes, coated with rabbit anti-human IgA immunoglobulin, followed by separation on Ficoll-Isopaque. Stable monoclonal lines were established by cloning in agarose. This shows that EBV-transformation is not restricted to the IgM-positive B cell category but can be extended to minority classes of B lymphocytes. The method provides the means to establish other minority categories as continuous lines, depending on the efficiency of the preselection procedure.
Delayed hypersensitivity in mice infected with reovirus. I. Identification of host and viral gene products responsible for the immune response.
Authors: Weiner H L , Greene M I , Fields B N
Published: December 2022

Delayed-type hypersensitivity (DTH) can be demonstrated in mice infected with reovirus by challenging primed animals in the footpad with virus. Maximal responses occur 7 days after immunization with as little as 10(5) viral particles. DTH to reovirus is transferable by lymph node cells and is mediated by T cells as the transfer of reactivity can be abrogated by treatment of cells with anti-Thy 1.2 plus complement. DTH to reovirus is serotype specific, animals infected with reovirus type 1 or 3 only develop DTH responses when challenged with the same serotype with which they were infected. Using recombinant viral clones containing genes from both parental serotypes, we have demonstrated that the S1 gene, the gene encoding the viral hemagglutinin, determines serotype specificity. Furthermore, in adoptive transfer experiments between mice of varying histocompatibility backgrounds, it was found that D or K, IA-IB region identity was required for the transfer of reactivity. These studies demonstrate that specific host and viral genes determine the in vivo cellular immune response to reovirus and should allow a more precise definition of the host cellular immune response to viral antigens.
Surface markers on the T cells that regulate cytotoxic T cell responses. II. Distribution of Ly 6.1 and Ly 7.2: selective expression of Ly 7.2 on helper T cell effectors.
Authors: Pilarski L M , Al-Adra A R , McKenzie I F
Published: December 2022

Helper T cells and suppressor T cells can be generated in vitro, yielding effector cells with radioresistant function that regulate a cytotoxic T cell response to alloantigen. The Ly 6.1 and Ly 7.2 antigen phenotype of these regulatory effector cells has been determined. Ly 7.2 was found to be selectively expressed on helper T cells; neither the suppressor cells nor the cytotoxic cells analyzed here were found to bear Ly 7.2 antigens. Mixing experiments demonstrated that the helper cell bears both Ly 1.1 and Ly 7.2. Removal of help by anti-Ly 7.2 treatment frequently enhanced suppressor activity. Suppressive activity was partially depleted by treatment with anti-Ly 6.1; helper cell activity was unaffected by such treatment. Cytotoxic T cell precursors bear neither Ly 6.1 nor Ly 7.2, but approximately half of the cytotoxic T cell effectors did bear Ly 6.1; none bore Ly 7.2. Analysis of populations depleted of 7.2-bearing cells should therefore allow the design of experiments that will increase our understanding of the interactions of various regulatory cell populations in the control of a cytotoxic T-cell response.
A peptide difference between the mu-chains from cell-associated and secreted IgM of the BCL1 tumor.
Authors: Yuan D , Uhr J W , Vitetta E S
Published: December 2022

The murine B cell tumor, BCL1, bears monomeric IgM lambda on its surface. After stimulation in vitro with LPS, the cells secrete pentameric IgM lambda. Comparison of mu-chains from radiolabeled intracellular, surface, and secreted IgM indicates that mu-chains from the three sites have different apparent m.w. Since the observed differences are analogous to those reported for normal murine lymphoid cells, the BCL1 cells were used for determining the structural basis for the differences in m.w. of mu-chains from the above sites. Comparative peptide analysis was performed on mu-chains from cell associated and secreted IgM. Approximately 25 peptides were identified after digestion with chymotrypsin and trypsin and analysis of peptides by cation exchange chromatography. All peptides co-eluted with the exception of a single extra peptide derived from the Fc portion of the secreted IgM. The same peptide was observed in a similar analysis using mu-chains from IgM secreted by normal splenocytes.
Isolation and characterization of calmodulin from a murine macrophage-like cell line.
Authors: Jamieson G A , Vanaman T C
Published: December 2022

Several lines of evidence implicate fluxes in the intracellular levels of CA++ and the cyclic nucleotiodes in the chemotactic, phagocytic, and cytotoxic responses of macrophages. Calmodulin, a ubiquitous small acidic Ca-binding protein, appears to link the intracellular second messengers--Ca++ and the cyclic nucleotides--through its ability to regulate numerous central metabolic enzymatic activities. A pure protein has been isolated and characterized from the macrophage-like cell line, P388D. This protein has been identified as calmodulin by demonstrating three of the Ca-dependent activities attributed to calmodulins. P388D calmodulin also has physiochemical properties similar to those of the previously characterized mammalian proteins. This study is the initial step of an examination of the role of this central regulatory protein in responses elicited by macrophages to external stimuli.
Production of a suppressor factor by human adherent cells treated with mycobacteria.
Authors: Wadee A A , Sher R , Rabson A R
Published: December 2022

Human peripheral blood mononuclear cell (MN) proliferation and lymphokine production induced by mitogen could be inhibited by heat killed whole mycobacteria. The inhibition was induced by a wide variety of mycobacteri but not by other Gram-positive or Gram-negative organisms or by latex particles. Proliferation and lymphokine production by adherent cell-depleted lymphocytes was not inhibited by these organisms. Adherent cells treated with mycobacteria had the ability to inhibit lymphocyte blastogenesis when co-cultured with the lymphocytes. the inhibitory effect of these adherent cells was due to the release of a heat stable, nondialyzable suppressor cells. These latter cells, which were T gamma cells, could inhibit the blastogenic ability of normal lymphocytes activated by mitogens. The results suggest that in situations of high mycobacterial load, adherent cells are activted to release a suppressor factor that will activate lymphocytes to become suppressor cells. This mechanism may explain the anergy associated with lepromatous leprosy or advanced tuberculosis.
A spatial association between membrane IgD and the receptor for C3b (CR1) at the cell surface of murine B lymphocytes.
Authors: Sitia R , Rabellino E M , Sockell M , Hämmerling U
Published: December 2022

Surface immunoglobulin D (SIgD) and receptors for C3b (CR1) were demonstrated to be closely associated at the surface of mouse spleen lymphocytes. When SIgD was modulated by incubation at 37 degrees C with heteroantisera (rabbit) or monoclonal alloantibodies specific for delta-chains, the number of splenocytes capable of forming rosettes with EAC1-3b decreased by about 40%, whereas a smaller effect (13%) could be observed when EAC1-3d (indicators for CR2) were used. Antibodies to surface IgM were not inhibitory, ruling out the possibility of nonspecific inhibition of the C receptor sites by antigen-antibody complexes formed at the cell surface. In addition, co-capping of IgD and cR1 was observed on 65% of the cells expressing both markers. In these experiments IgM was shown to redistribute independently from both CR1 and CR2. CR2 and IgD also capped independently. Taken together with the observations that IgD and CR are ontogenetically related and that they have in common certain biologic properties (such as sensitivity to proteolytic enzymes and rate of turnover), these data suggest a functional relationship between the 2 surface receptors. A possible role in the mechanism of B lymphocyte triggering is discussed.
Allelic forms of anti-phosphorylcholine antibodies.
Authors: Lieberman R , Rudikoff S , Humphrey W , Potter M
Published: December 2022

Anti-idiotype antisera were prepared to 2 phosphorylcholine (PC) binding myeloma proteins, T15 of BALB/c origin and C3 of C57BL origin. These antisera were shown to recognize the respective determinants on induced anti-PC antibodies in the 2 parental strains. Genetic analysis of these V region markers in backcross progeny of (BALB/c X C57BL/6) X BALB/c demonstrated that the 2 determinants segregated as simple Mendelian alleles linked to the allotype locus. The genetic data are consistent with previously reported structural studies suggesting the allelic nature of the T15 and C3 heavy chain variable regions. The expression of the T15 and C3 antigenic determinants in Ig congenic and recombinant inbred strains derived from BALB/c-C57BL/6 crosses further supports the concept of allelism although a single exception was observed. Strain distribution analysis has indicated the potential existence of other alleles of the T15 gene in addition to C3.
Alloreactive cloned T cell lines. II. Polyclonal stimulation of B cells by a cloned helper T cell line.
Authors: Glasebrook A L , Quintans J , Eisenberg L , Fitch F W
Published: December 2022

A cloned helper T cell line, L2, has been derived that promotes the proliferation of cytolytic T cells with the concomitant expression of cytolytic activity. L2 helper cells also cause a polyclonal stimulation of B cells in the absence of antigen, as measured by the number of total plaque-forming cells (PFC) as well as those generated toward TNP or SRBC. The L2 helper cell function is dependent on cell number, is radioresistant, and is mediated via soluble factor(s). Maximum levels of PFC were generally observed after 4 days of culture, with IgM-secreting B cells being predominantly induced in these cultures. Both the proliferation of and stimulation by L2 helper cells are activated by Misa determinants. F1 progeny from a mating of CBA/N and DBA/2 (Mlsa) that did not bear Mlsa (NDF1) were nonstimulatory, whereas those F1 animals bearing Mlsa (DNF1) induced L2 helper-cell proliferation and function. L2 helper-cell recognition of Mlsa determinants present on the responding B cell surface was not required for polyclonal helper-dependent stimulation in vitro. L2 cells stimulated polyclonal antibody secretion in syngeneic as well as allogeneic B cells. Since Mls antigens are not expressed on T cells, these results indicate that regulatory T cell circuits are initiated by non-T cells, possibly B cells.
Regulation of macrophage populations. II. Synthesis and expression of Ia antigens by peritoneal exudate macrophages is a transient event.
Authors: Beller D I , Unanue E R
Published: December 2022

We have evaluated the biosynthesis and surface expression of I-A antigens by peritoneal macrophages and found that both events terminated during the 1st day in culture, in contrast to the undiminished synthesis and expression of H-2K antigens. This pattern was observed regardless of the means by which the macrophages were elicited, but was subject to modulation for a limited period of time in vitro: phagocytic stimuli were able to augment both I-A synthesis and expression. The loss of I-A and the re-expression after phagocytosis were both reflected in the stimulatory capacity of these macrophages in the mixed leukocyte reaction. Moreover, we found that I-A-bearing macrophages were lost from the exudate in vivo after irradiation. Our data suggest that, as in vitro, this phenomenon is due to the transition of individual macrophages from I-A-positive to I-A-negative, and that constant renewal is required to maintain the I-A-bearing subset in vivo.
Identification and separation by bacterial adherence of human lymphocytes that suppress natural cytotoxicity.
Authors: DeBoer K P , Kleinman R , Teodorescu M
Published: December 2022

Human lymphocyte subpopulations (B1, B2T1, T2T3, and T4, our denomination) have been previously identified by bacterial adherence, and differences in functions (mitogen responses, specific cytotoxicity, and natural killing activity) have been associated with some of these subpopulations. The natural killing activity (NK) was located in the T4 lymphocyte subpopulation. Here we investigated the possibility that lymphocytes capable of suppressing the NK activity of the T4 cells could be identified and isolated from one of the other lymphocyte subpopulations. Freshly isolated, monocyte-depleted human peripheral blood lymphocyte (PBL) were separated into adherent and nonadherent cells after centrifugation against various bacterial monolayers. The PBL and the resulting subpopulations of PBL were tested as effector cells in a 4-hr cytotoxicity assay against the CEM lymphoblastoid cell line. The addition of viable T2 lymphocytes to either PBL or T4 lymphocytes resulted in a significant decrease in NK activity, whereas no decrease was seen when T1, T1T3, or killed T1T2 cells were added. This decrease in NK activity was not due to a simple dilution of the active NK cells, to alteration of the lymphocytes by their processing on the bacterial monolayers, or to a competition for binding to the target cells. We concluded that the T2 lymphocyte subpopulation contains the cells capable of suppressing the ability of normal human peripheral blood lymphocytes (T4 subpopulation) to perform natural killing.
Cell-mediated immunity to herpes simplex virus: induction of cytotoxic T lymphocyte responses by viral antigens incorporated into liposomes.
Authors: Lawman M J , Naylor P T , Huang L , Courtney R J , Rouse B T
Published: December 2022

The immunogenicity of inactivated herpes simplex virus type 1 (HSV-1) antigens incorporated into liposomes was measured by their ability to induce secondary anti-HSV-1 specific cytotoxic T lymphocyte (CTL) responses in splenocyte cultures from virus-primed mice. Such virus-specific CTL could be induced provided the liposomes contained virus along with plasma membrane antigen of the same H-2 type as that of the virus-primed responser cells. Responses did not occur in cultures stimulated with liposomes containing only viral antigens or with a mixture of liposomes composed respectively of lipid and virus with those composed of lipid and plasma membrane proteins. Moreover F1 responder cells stimulated with liposomes composed of virus and plasma membrane protein of one of the parental haplotypes produced CTL restricted in their cytotoxicity to infected targets of the same haplotype as was used in the liposome. These results show that liposomes can be used to induce anti-HSV-1 CTL with inactivated viral antigens but recognition of both viral and H-2 antigen is required for this process to occur in vitro. The implications of our findings to the preparation of subunit vaccines against HSV-1 are briefly discussed.
Dichotomies in the reactivity to worm antigen in human schistosomiasis mansoni.
Authors: Ellner J J , Olds G R , Osman G S , El Kholy A , Mahmoud A A
Published: December 2022

3H-thymidine incorporation was studied using peripheral blood mononuclear cells (PBMC) from 41 Egyptians with Schistosoma mansoni infection. The individuals were preselected to fall into 3 age-matched categories: asymptomatic with light and heavy infections and those with schistosomal hepatosplenomegaly. Seven uninfected individuals served as controls. PBMC from all groups were comparable in their responsiveness to phytohemagglutinin (PHA), streptokinase-streptodornase (SKSD), and the schistosome soluble egg antigen (SEA). However, DNA synthesis induced by soluble worm antigenic preparation (SWAP) differed significantly among these groups. The mean response to SWAP (delta cpm = experimental cpm minus control cpm +/- standard error) was markedly decreased in individuals with heavy infections (1,963 +/- 509) compared with those with light to moderate egg excretion (4,646 +/- 790; p less than 0.01). Moreover, 2 subgroups were discernible among patients with hepatosplenomegaly. Seven were unresponsive to SWAP (7659 +/- 231), whereas 13 had vigorous responses (14, 617 +/- 2263; p < 0.01). This is the first demonstration of an inverse relationship between specific immune responsiveness to adult worm antigens and intensity of infection in humans with schistosomiasis mansoni. The depressed lymphocyte reactivity in patients with heavy infection, whether cause or consequence of the parasite load, may perpetuate large worm burdens. Furthermore, the observations on patients with hepatosplenomegaly may reflect differing pathogenetic mechanisms.
C5a-induced tracheal contraction: effect of an SRS-A antagonist and inhibitors of arachidonate metabolism.
Authors: Regal J F , Pickering R J
Published: December 2022

C5a, a peptide derived from the fifth component of complement, has been shown to cause significant prolonged smooth muscle contraction in isolated guinea pig trachea. This contraction was not affected by the antihistamine diphenyhydramine. To assess further the potential role that C5a may play in allergic bronchospasm, we investigated the role of products of arachidonate metabolism in the C5a-induced tracheal contraction. 5,8,11,14-Eicosatetraynoic acid, an inhibitor of lipoxygenase and cyclooxygenase, virtually eliminated the tracheal contraction induced by C5a. The prostaglandin synthesis inhibitor, acetylsalicylate, did not inhibit the C5a-induced tracheal contraction and enhanced the tracheal response to acetylcholine. FPL 55712, an antagonist of slow reacting substance of anaphylaxis (SRS-A), almost completely inhibited the tracheal response to C5a and at higher concentrations employed, FPL 55712 also inhibited the tracheal response to exogenous prostaglandin F 2 alpha. These studies indicate that C5a-induced tracheal contraction is mediated by a product or products of arachidonate metabolism, and is, at least in part, mediated by SRS-A.
Mechanism of NK cell activation: relationship between Qa5+ NK cells and lymphocytes.
Authors: Chun M , Fernandes G , Hoffmann M K
Published: December 2022

Interferon (IF) induces within 20 hr of incubation Qa5+Thy-1- NK cells but Qa5-Thy-1+ cytotoxic cells in cultures of murine splenocytes. The mechanism of Qa5+ NK cell activation has been studied by using tumor necrosis serum (TNS), concanavalin A (Con A), and lipolysaccharide (LPS) as additional NK cell-inducing reagents. It was found that IF and TNS activate precursor NK cells directly without the involvement of accessory cells. The T cell mitogen Con A and the B cell mitogen LPS, on the other hand, induced Qa5+ NK cells only in the presence of lymphocytes. Con A-stimulated T cells and LPS-stimulated B cells release factors into the culture medium that activate Qa5+ NK cells. Since Con A and LPS are known to be interferon inducers, it is inferred that Con A-induced and LPS-induced activation of NK cells is mediated by IF. The data demonstrate that NK cells become activated as a consequence of lymphocyte activation and thus suggest a relationship between lymphocyte dependent- and NK cell-dependent defense systems. This relationship is also implied by observations made with NZB mice. NZB mice lose NK cell activity at the time when they develop autoimmune diseases.
Sensitization of lymphocytes against pooled allogeneic cells. II. Characterization of effector cells cytotoxic for autologous lymphoblastoid cell lines.
Authors: Zarling J M , Bach F H , Kung P C
Published: December 2022

Stimulation of human lymphocytes in mixed leukocyte culture (MLC) with x-irradiated pooled allogeneic normal cells (poolx) was previously shown to result in generation of effector cells cytotoxic for autologous Epstein-Barr virus- (EBV) transformed lymphoblastoid cell lines (LCL). This study was undertaken to determine whether lysis of the autologous EBV- transformed LCL cells by pool-stimulated cells is mediated by cytotoxic Tc lymphocytes (Tc) or natural killer- (NK) like cells, both of which are generated in MLC. In the first series of experiments, proliferating cells were eliminated by treatment of pool-stimulated cells with 5 X 10(-5) M 5-bromodeoxyuridine (BUdR) and light. The remaining cells failed to lyse allogeneic normal lymphocytes and autologous LCL cells, whereas cytotoxicity against NK-sensitive K562 leukemia cells was retained. In the second series of experiments, pool-stimulated effector cells were treated with monoclonal anti-human Tc cell antibodies, OKT3 or OKT8, and complement (C). The cells recovered after antibody and C treatment were diminished in their ability to lyse allogeneic normal lymphocytes as well as autologous LCL cells, whereas their cytotoxicity against K562 leukemia cells was unaffected. These combined results provide strong evidence that lysis of autologous LCL cells by lymphocytes stimulated with pooled allogeneic normal cells is mediated by Tc rather than NK-like cells.
Influence of IgH V-region genes on the growth kinetics of a murine B cell leukemia (BCL1).
Authors: Ciavarra R , Forman J
Published: December 2022

The growth kinetics of an IgM-bearing B cell leukemia of BALB/c (Ig-1a) origin, designated BCL1, has been investigated in 2 allotype immunoglobulin (Ig) heavy (H) chain congenic strains, C.B-20 (Ig-1b) and C.AL-20 (Ig-1d), and an (H) chain recombinant strain, BAB-14 (Ig-1a/1b), that carries Ig-1a genes in the variable (V)-region and Ig-1b genes in the constant (C)-region. When large numbers (10(6) to 10(7)) of BCL1 cells were injected into these mice, leukemia, as measured by the appearance of leukemic cells in peripheral blood with subsequent mortality, did not occur in C.B-20, was delayed in C.AL-20, and progressed at the same rate in BAB-14 relative to BALB/c control mice. These results indicate that an immune response directed against an antigen encoded for by an H chain V region gene (idiotype or variable-region allotype) or linked gene (minor histocompatibility antigen) prevents the growth of the BCL1 leukemia in the C.B-20 mice. Tumor resistance appears to be due to T cell activity since adoptive transfer of such cells from C.B-20 tumor rejectors protected sublethally irradiation recipients from subsequent tumor challenge. Although H-2 restricted, anti-BCL1 cytotoxic cells were detected in C.B-20 mice challenged in vivo and restimulated in vitro with BCL1 cells, evidence is discussed that suggests that the resistance observed is not due to these effector cells. The resistance of allotype congenic mice to BCL1 was not absolute; a small inoculum (10(2)) was as lethal in C.B-20 and C.AL-20 as BALB/c mice. Thus, Ig-encoded cell surface antigens, although immunogenic, in no way ensure ultimate host survival.
B cell repertoire ontogeny: heritable but dissimilar development of parental and F1 repertoires.
Authors: Cancro M P , Klinman N R
Published: December 2022

This study examines the genetics of antibody repertoire ontogeny by the comparison of the repertoires in B10.D2, BALB/c, and (BALB X B10.D2)F1 mice at 12 to 14 days of age. This was accomplished by fine specificity analysis of clonotypes responsive to the influenza virus hemagglutinin in each strain. The results indicate that: a) neonatal antibody repertoires are in general less heterogeneous than their adult counterparts, which confirms and extends previous observations and reinforces the assertion that repertoire ontogeny is a heritable, patterned process; b) the BALB/c and B10.D2 neonatal repertoires differ from one another in clonotype compositions, facilitating genetic analyses of repertoire establishment; c) the BALB/c X B10.D2)F1 neonatal repertoire, although of restricted heterogeneity, is clearly dissimilar from either parental repertoire. These findings indicate that B cell repertoire ontogeny may be governed by heritable factors that interact with but are not necessarily themselves variable region structural genes. Furthermore, it appears that the expressed responsive B cell repertoire is a selected subset of the inherited potential repertoire.
Human endothelial culture supernatant (HECS): evidence for a growth-promoting factor binding to hybridoma and myeloma cells.
Authors: Astaldi G C , Janssen M C , Lansdorp P M , Zeijlemaker W P , Willems C
Published: December 2022

Human endothelial culture supernatant (HECS) contains a factor(s) that enhances the proliferation of hybridoma cells as we reported previously. In the present paper, we found that, in comparison with endothelial cells, their supernatant exerts a much stronger growth-promoting effect on hybridoma cells, which can also be detected earlier. In a confluent culture of endothelial cells, detectable amounts of this factor(s) are produced after 2 hr of incubation, and the production is linear in time for 3 days. The enhancing effect of HECS on the proliferation of hybridoma cells appears to be independent of the concentration of cells in the culture. The activity of HECS is adsorbed to hybridoma or myeloma cells, but not to thymocytes. HECS acts on hybridoma cells by delivering a growth-promoting signal that induces the hybridoma cells to proliferate.
Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. II. Characterization of a soluble suppressor of B cell immunoglobulin production.
Authors: Fleisher T A , Greene W C , Blaese R M , Waldmann T A
Published: December 2022

Human peripheral blood mononuclear cells (PBMC) activated with the mitogenic lectin concanavalin A (Con A) elaborate a soluble immune suppressor supernatant (SISS) that contains at least 2 distinct suppressor factors. One of these, SISS-B, inhibits polyclonal B cell immunoglobulin production whereas the other, SISS-T, suppresses T cell proliferation to both mitogens and antigens. The latter mediator is discussed in the companion paper. Characteristics of the human soluble suppressor of B cell immunoglobulin production (SISS-B) include: 1) inhibition by a noncytotoxic mechanism, 2) loss of activity in the presence of the monosaccharide L-rhamnose, 3) appearance within 8 to 16 hr after the addition of Con A, 4) elaboration by cells irradiated with 500 or 2000 rads, 5) production by highly purified T cells, 6) stability at pH 2.5 but instability at 56 degrees C, and 7) m.w. of 60 to 80,000. These data indicate that after Con A activation, selected T cells not only become potent suppressor cells, but also generate a soluble saccharide-specific factor(s) that inhibits polyclonal immunoglobulin production by human B cells.
Expression of endogenous retroviral envelope antigen in Ig(+) B cells of immunized 15I5 X 71 chickens.
Authors: Halpern M S , Mason W S , Ewert D L , Deery D T , England J M
Published: December 2022

In a previous study (1), we observed that antigen cross-reactive with structural protein of the endogenous retrovirus RAV-O is expressed in splenic Ig(+) B lymphocytes of immunized 15I5 X 71 chickens. The present experiments were undertaken to determine the relationship of this antigen to viral gag- and env-coded antigenic specificities. As analyzed by immunofluorescence with several antisera, group-specific determinants of the gp85 envelope glycoprotein as well as viral-related type E-specific determinants were detectable in islands of Ig(+) splenocytes; antigenic determinants of viral gag protein were not detected in the splenic islands. These observations indicated that antigen cross-reactive with endogenous retroviral envelope glycoprotein is expressed in Ig(+) B cells.
Purification to apparent homogeneity of murine interleukin 1.
Authors: Mizel S B , Mizel D
Published: December 2022

Interleukin 1 was purified to apparent homogeneity from the culture fluid of P388D1 cell line macrophages by a procedure involving ammonium sulfate fractionation, phenyl Sepharose and Ultrogel AcA54 chromatographies, and preparative isoelectrofocusing. The interleukin 1 was purified more than 300-fold to a specific activity of approximately 1 X 10(6) U/mg protein. The purified interleukin 1 exhibited microheterogeneity. Three charge species, which we have termed alpha, beta, gamma, were resolved by Tris-glycinate discontinuous polyacrylamide gel electrophoresis. The partial amino acid content of the alpha species of interleukin 1 was determined. On the basis of the purification data, it appears that interleukin 1 is biologically active within the 10(-11) to 10(-10) M concentration range. The success of the purification was due in part to the use of a superinduction protocol that resulted in the production of interleukin 1 at a rate of approximately 1 microgram/24 hr/4 X 10(6) P388D1 cells.