bluuebunny/crossref_metadata_2025 huggingface dataset:
H-2-Nonrestricted Cytotoxic Responses to an Antigen Encoded Telomeric to H-2D
Authors: Kastner Daniel L. , Rich Robert R.
Published: January 2023

Cytotoxic T lymphocytes (CTL) were generated in secondary in vitro cultures against H-2-identical allogeneic stimulators. In some strain combinations, such as C57BL/10 (B10) responding to C3H.SW, cytolysis was restricted to target cells bearing the H-2 antigens of the immunizing strain. However, B10.BR effectors sensitized to C3H, AKR, or CBA efficiently lysed targets of several H-2 haplotypes, including B10 targets congenic with the B10.BR responders. The activity of these CTL was totally abrogated by anti-Thy 1.2 plus complement. Lysis of 51Cr-labeled B10 targets by B10.BR anti-AKR CTL was inhibited by unlabeled B10 and AKR targets equally well, thus showing that the clones killing B10 are included in the AKR-specific clones. In addition, both B10 and B10.D2 stimulator cells were effective in the in vitro boosting of the B10.BR anti-AKR cytotoxic response. Mapping experiments using B10, B10.A, B10.A(2R), B10.A(5R), C57BL/6, and B6-Tlaa mice indicated that the locus relevant to these phenomena maps to the right of H-2D. Since both Con A and LPS blast targets were susceptible to the activity of the nonrestricted CTL, antigens encoded by this locus are not unique to the T or B cell lineage.
Serum Expression of a VK Structure, VK-11, Associated with Inulin Antibodies Controlled by Gene(s) Linked to the Mouse IgCH Complex
Authors: Slack John H. , Shapiro Marjorie , Potter Michael
Published: January 2023

Inulin, β(2 → 1) linked fructofuranan, antibodies (INU-Ab), and a cross-specific idiotype, VK-11, present on the κ-chain of BALB/c inulin-binding myeloma proteins (INUBMP) are detected in mouse serum by solid phase radioimmunoassay systems. BALB/c normal serum contained 5 to 6 μg of VK-11 and INU-Ab/ml, whereas serum from bacterial levan-immunized BALB/c contained 28 to 30 μg of VK-11 and INU-Ab/ml. In contrast, serum from normal and immunized C57BL/6N contained less than 0.25 and 1.0 μg of VK-11 and INU-Ab/ml, respectively. Although not detected in serum by radioimmunoassay technique, INU-Ab was absorbed from large volumes of ascites induced in C57BL/6N by the Tung-Nisonoff method that contained the VK-11 idiotype. INU-Ab and VK-11 levels comparable to BALB/c were found in the Ig congenic strain BC-8 carrying the BALB/c allotype and low-intermediate levels were found in the Ig congenic strain CB-20 (C57BL/6N allotype). INU-ab and VK-11 serum levels comparable to BALB/c were observed in the Bailey RI strains C×BG and C×BJ (BALB/c allotype) whereas the RI strains C×BD (E, H, I and K) with the C57BL/6N IgCH had INU-Ab and VK-11 serum levels comparable to C57BL/6N. Since the BC-8 with the C57BL/6N CK-VK complex must have the VK-11 gene, the BALB/c-C57BL/6N VK-11 strain difference cannot be due to a polymorphism in a VK-11 structural gene. Other genes linked to IgCH appear to control VK-11 and INU-Ab serum expression. Possibly, allelic polymorphism in the VH-5 homolog influences the affinity of the VH-5-VK-11 determined binding site for β(2 → 1) fructofuran and hence the maturation of INU-Ab B cell clones. Alternatively, INU-Ab expression may be regulated by non-Ig structural genes linked to the mouse IgCH complex locus.
Suppressor Cell Induction in Vitro
Authors: Kontianen Sirkka , Howie Sarah , Maurer Paul H. , Feldmann Marc
Published: January 2023

The capacity of responder and nonresponder strains of mice to generate suppressor cells and factors to two antigens under MHC linked Ir gene control was investigated. Eight different H-2 types (H-2b,d,f,k,p,q,r,s) as well as seven independently derived strains (B10, BALB/c, CBA/Ca, A/St, DBA/2, P/J, SJL) were tested, and all yielded suppressor factor (SF) to (T,G)-A--L and GAT. This indicated that the genetic control of SF production was different from that of helper cell induction. Unlike previous reports of GAT suppressor extracts the GAT-specific suppressor factors acted equally on both responder and nonresponder strains. As reported earlier with in vitro induced protein- (KLH) specific suppressor factors, GAT and (T,G)-A--L specific suppressor factors failed to show any genetic restriction in their function. The implications of these results for the general mechanism of Ir gene control are discussed.
Serologically Defined Subpopulations of Human T Lymphocytes
Authors: Brouet Jean-Claude , Chevalier Annette
Published: January 2023

Several rabbit antisera to T cells obtained from various sources (thymus, peripheral blood, brain, T-derived leukemias) were studied with the aim to obtain reagents specific for a subset of T cells. Sera were first absorbed on human tissues and B cells; thereafter these T cell-specific sera were additionally absorbed with T cells of different origin and especially with leukemic T cells, which are likely to represent a clonal expansion of a subset of T cells with potentially unique antigenic markers. Three antigenically distinct subpopulations of T cells were delineated. The relationship of these subsets with previously defined human T cell subpopulations (T subsets with a receptor for the Fc or IgG or IgM or with a receptor for a lectin from wheat germ agglutinin) was investigated.
Demonstration of Hepatitis B e Antigen in the Core of Dane Particles
Authors: Takahashi K. , Akahane Y. , Gotanda T. , Mishiro T. , Imai M. , Miyakawa Y. , Mayumi M.
Published: January 2023

Dane particles were isolated in a large scale from plasma of asymptomatic carriers of hepatitis B surface antigen. The core of Dane particles was exposed by treatment with NP-40 and 2-mercaptoethanol. The antigenicity of hepatitis B e antigen (HBeAg) was not detected on the surface of Dane particles or of their cores. However, when Dane particle cores were treated with Pronase, some activity of HBeAg was liberated from them as a small molecule. When the cores were further treated with SDS, they revealed a high activity of HBeAg, indicating that HBeAg existed in the core of Dane particles in a cryptic form, which can be exposed by treatment with proteolytic enzyme or SDS. Dane particles and their cores were subjected to polyacrylamide gel electrophoresis in SDS. After electrophoresis, the gel was cut into two halves, and each half was determined for polypeptide composition and for HBeAg activity. Both of Dane particles and their cores disclosed two peaks of HBeAg activity associated with molecules with a size of 19,000 and 45,000 daltons. These two polypeptides were the major constituents of the cores. Dane particles revealed several polypeptides in addition to the HBeAg polypeptides, which were identified as hepatitis B surface antigen components. On the basis of the results obtained, HBeAg is an integral component of Dane particles, the presently accepted hepatitis B virions. These results provide the basis for the close correlation between HBeAg and Dane particles in the serum of persons infected with hepatitis B virus.
Ascaris and Eosinophil
Authors: Tanaka Jiro , Baba Toru , Torisu Motomichi
Published: January 2023

In the previous study, we found an eosinophil chemotactic factor of the parasite (ECF-P) in extracts from the body cavity fluid of the Ascaris species. In this study, the physicochemical characteristics of ECF-P were determined in order to elucidate the relationship between ECF-P and Ascaris antigens. ECF-P was active in both in vivo and in vitro chemotactic assay systems and was found to be heat labile, nondialyzable, and stable to lyophilization. The estimated m.w. was approximately 30,000 daltons. The isoelectric point of ECF-P was 8.5. It was quite different from the Ascaris antigen in the same extract, or various Ascaris allergens that had been reported previously by other researchers. Furthermore, ECF-P did not show any activity in eliciting a guinea pig passive cutaneous anaphylaxis (PCA) reaction. From these experimental results, we concluded that ECF-P is not identical to Ascaris antigens.

In addition, we found that the neutrophil chemotactic factor of the parasite (NCF-P), with at least two components, is present in the Ascaris extract, and is also heat labile and resistant to dialysis and lyophilization, but separable from coexistent ECF-P by reason of their different physicochemical properties.
Maturation of B Lymphocytes
Authors: Lala P. K. , Johnson G. R. , Battye F. L. , Nossal G. J. V.
Published: January 2023

The relationship between the surface IgM (S-IgM) density and Ia antigens or total S-Ig density and the ability to produce B lymphocyte colonies (BL-C) in agar was examined for small lymphocyte populations in adult CBA bone marrow and spleen. Lymphocyte fractions with various levels of S-IgM sorted by the fluorescence-activated cell sorter (FACS) were relabeled for Ia antigens with a 125I-labeled Protein A sandwich technique. Similar fractions sorted by the FACS on the basis of different S-Ig levels were grown in agar for generating BL-C. Most or all S-IgM-bearing cells, including those with the lowest S-IgM levels, were found to be Ia + ve in both organs. Thus a lag, if any, between S-IgM acquisition and Ia acquisition by the B cells in the adult marrow must be small. Secondly, the Ia density of Ia + ve cells increased in parallel with IgM density in both the organs, indicating a strong functional association between the two surface markers. Most BL-C-forming cells (BL-CFC) were found to be included in the S-Ig + ve class, but the BL-CFC incidence within this class increased with increasing S-Ig density, possibly suggesting a parallel increase in the putative mitogen receptors on B cells. Null (S-Ig - ve, θ - ve) lymphocytes both in the marrow and the spleen showed a small proportion of Ia + ve cells as well as a small incidence of BL-CFC; these subsets remain to be characterized further. These studies reveal that B cell maturation in the adult animal is associated with a concurrent appearance of increasing Ig, Ia, and mitogen responsiveness.
Generation of Cytolytic T Lymphocytes in Vitro
Authors: Maryanski Janet L. , Cerottini Jean-Charles , Brunner K. Theodor
Published: January 2023

Short-term (15 min) sodium periodate (NaIO4) treatment of mouse spleen cells previously primed in vivo or in vitro against alloantigens induced the formation of secondary (2°) cytolytic T lymphocytes (CTL) specific for the priming antigens. CTL formation was readily demonstrable within 24 hr after treatment. This early CTL response occurred equally well in the presence or absence of cytosine arabinoside (Ara C), indicating that NaIO4 could induce CTL independently of DNA synthesis. Forty-eight hours after periodate treatment, the lytic activity was similar to that observed in parallel cultures stimulated with irradiated allogeneic spleen cells, although the peak activity was reached earlier (day 4) and was somewhat lower than that induced by alloantigen. The addition of irradiated NaIO4-treated unprimed syngeneic spleen cells to cultures of untreated alloimmune spleen cells also led to CTL formation, which suggests an indirect mechanism of activation. In contrast to alloimmune spleen cells, normal spleen cells treated with NaIO4 developed only very low levels of cytotoxicity after 4 days of incubation. However, in the presence of PHA, such cells were capable of lysing syngeneic and allogeneic target cells.
Inhibition of Complement-Mediated Lysis of Sheep Erythrocytes by Cell-Free Preparations from Streptococcus Mutans BHT
Authors: Silvestri Louis J. , Knox Kenneth W. , Wicken Anthony J. , Hoffmann Edward M.
Published: January 2023

A cell-free extract from the spent medium of Streptococcus mutans BHT was tested for anti-complementary activity with sheep erythrocytes (E) as target cells. It was determined that this extract was enriched for extracellular lipoteichoic acid (LTA) and that the LTA bound to the surfaces of sheep E. Furthermore, sheep E, sheep E plus antibodies (EA), and sheep cells in the intermediate stage of complement (C) component fixation EAC14̅ became refractory to C-mediated lysis after treatment with the LTA-rich extract. Sheep E in the intermediate states and were unaffected despite the fact that LTA could be detected on the surfaces of these cells with the passive hemagglutination procedure. Preliminary results showed that the C inhibitory activity co-purified with LTA, and LTA (both crude and purified) from other bacteria were anticomplementary. Both crude extracellular material from S. mutans BHT and partially purified extracellular LTA from the same bacteria caused consumption of whole human C activity.
A Receptor for IgA on Human T Lymphocytes
Authors: Lum L. G. , Muchmore A. V. , Keren D. , Decker J. , Koski I. , Strober W. , Blaese R. M.
Published: January 2023

Receptors for IgA antibody-antigen complexes were demonstrated on 2 to 18% (mean 6.7%) of human peripheral blood T cells. The proportion of cells bearing detectable IgA receptors was low in freshly prepared T cells and increased in number after 18 to 24 hr of culture similar to the time course of appearance of the Tμ receptor. These T receptors were shown to be distinctly different from Fc-IgM and Fc-IgG receptors on T cells by blocking studies with purified IgA, IgG, and IgM.
Role of Thymic Hormone (THF) and of a Thymic Plasma Recirculating Factor (TPRF) in the Modulation of Human Lymphocyte Response to Pha and Con A
Authors: Rotter Varda , Trainin Nathan
Published: January 2023

The results presented here point to the possibility that calf thymus extracts contain, in addition to the thymic hormone (THF), a second component: thymic plasma recirculating factor (TPRF). THF, which is involved in the process of T cell maturation and has been characterized as a protein of m.w. 3000 eluted in the void volume of a G-10 Sephadex column (G-10-I), caused an increased level of intracellular cAMP in umbilical cord blood lymphocytes (UCBL). This is in agreement with our previous observation that THF plays a major role in the differentiation of T cells. The second active material, TPRF, also isolated from thymic extract, is of a molecular size below 500 and was eluted in a G-10 Sephadex column at the fourth protein peak; it seems to circulate in the blood. Previously, we had observed an impaired response of UCBL to PHA and Con A stimulation in the presence of dialyzed human plasma (DHP). Our present results indicate that this impaired response is restored exclusively by TPRF. A factor with TPRF-like activity was also isolated from the plasma of normal donors; yet it was not detected in the plasma of thymectomized patients suffering from myasthenia gravis (MG). This suggests that TPRF from plasma is thymus dependent. TPRF does not affect the level of intracellular cAMP in UCBL.
Macrophage Factor Controlling Differentiation of B Cells
Authors: Hoffmann M. K. , Koenig S. , Mittler R. S. , Oettgen H. F. , Ralph P. , Galanos C. , Hammerling U.
Published: January 2023

Peritoneal macrophages of the mouse produce, in response to cell wall components of Gram-negative bacteria (lipopolysaccharide and lipoproteins), a factor that causes antigen-stimulated B cells to differentiate into antibody-producing cells. Unlike lipopolysaccharide, this factor is not mitogenic for B cells. Production of the macrophage factor does not depend on participation of T cells or other accessory cells since it is readily produced by several cloned macrophage cell lines as well as by peritoneal macrophages of athymic nude mice. The factor is active only in conjunction with antigen. T cells, although apparently not necessary, amplify its effect. The factor induces phenotypic differentiation of B cell precursors as selectively as thymopoietin induces differentiation of prothymocytes.
The Human Secretory Immune System Shows Striking Heterogeneity with Regard to Involvement of J Chain-Positive IgD Immunocytes
Authors: Brandtzaeg P. , Gjeruldsen S. T. , Korsrud F. , Baklien K. , Berdal P. , Ek J.
Published: January 2023

Although gland-associated immunocyte populations normally contain a preponderance (67 to 91%) of IgA-producing cells, the proportion of the other immunocyte classes varies much among different glandular sites and from case to case. Especially notable is the relatively high percentage of IgM cells (18%), and the virtual absence of IgD cells in jejunal mucosa. Conversely, IgD-producing immunocytes amount, on the average, to 2.5% in parotid gland and to 9 to 10% in lacrimal and nasal glands.

These differences were amplified in patients who completely lacked IgA cells; their gastro-intestinal mucosa contained a preponderance (56 to 91%) of IgM-producing cells, whereas the comparable specimens of nasal, lacrimal, and parotid glands contained mainly IgD-producing cells (51 to 82%) along with a smaller proportion of IgM cells (7 to 21%). The number of IgG cells was within the range of 9 to 41%, regardless of the glandular site, but amounted to 98% in a nonglandular mucosal specimen (gingiva) available from one of the patients. The total number of Ig-producing cells per glandular tissue unit (immunocyte density) was in the IgA-deficient patients generally within the ranges observed for control subjects containing normal local IgA-cell populations.

It is concluded that an IgA-producing capacity of B cells is no requirement for their homing to glandular sites and subsequent local maturation. The results, instead, indicate that the usual predominance of IgA-producing immunocytes found in such sites merely reflects normal differentiation pathways taken by fairly immature B cells. The prominent J chain-synthesizing capacity shown by IgD- and even by IgG-producing cells accumulating in glandular sites in IgA deficiency most likely reflects that they belong to B cell clones in an early phase of differentiation, as has previously been suggested for IgA precursor cells homing to such sites.
In Vitro Studies of Antigen-Induced Bronchospasm: Effect of Antihistamine and SRS-A Antagonist on Response of Sensitized Guinea Pig and Human Airways to Antigen
Authors: Adams G. Kenneth , Lichtenstein Lawrence
Published: January 2023

Exposure of sensitized guinea pig tracheal rings or human bronchial strips to specific antigen in vitro resulted in a rapidly developing, prolonged contraction that was resistant to washing. Treatment of the tissue with diphenhydramine, a histamine H1 antagonist, before antigen delayed the onset and decreased the amplitude of the initial phase of the contraction but did not reduce the duration. Diphenhydramine treatment after development of the contraction did not relax the airway tissue. Antigen-induced histamine release from guinea pig trachea and from human bronchus was complete within the initial 15% of the duration of the contraction. Treatment of sensitized airway tissue with FPL 55712, a SRS-A antagonist, before antigen selectively inhibited the prolonged phase of the response. FPL 55712 administration after the development of antigen-induced contraction resulted in relaxation. These data suggest that both histamine and SRS-A are involved in the response of sensitized guinea pig and human airway tissue to antigen, with histamine mediating the early phase of the contraction and SRS-A primarily mediating the protracted phase.
Characterization of in Vitro T-Lymphocyte Colonies from Spleens of Nude Mice
Authors: Jacobs Stanley W. , Miller Richard G.
Published: January 2023

Cells residing in the spleens of nude mice that appear Thy-1 negative can give rise to Thy-1 positive colonies in an in vitro culture system. Cells from pooled colonies can provide an accessory cell required for the development of cytotoxic lymphocytes from their precursors in an in vitro mixed lymphocyte reaction. As few as 50 such colony cells produce detectable activity.
Anti-β2-Microglobulin Lymphocytotoxic Autoantibodies in Systemic Lupus Erythematosus
Authors: Revillard Jean-Pierre , Vincent Claude , Rivera Sergio
Published: January 2023

The occurrence of anti-beta-2-microglobulin (β2m) lymphocytotoxic antibodies was investigated in 81 sera obtained from 63 patients with systemic lupus erythematosus (SLE). β2m-binding activity, measured by precipitation of radiolabeled β2m in polyethylene glycol, was found significantly higher in SLE than in control sera. Chromatography of SLE sera on polyacrylamideagarose gel AcA 3/4 showed that most of the β2m-binding activity was recovered in the IgG peak. This activity could be adsorbed on staphylococcal protein A-Sepharose immunosorbent. Complement-dependent lymphocytotoxicity was detected at 15°C in 32 SLE sera, of which 19 could be inhibited by addition of 1 ng β2m. A strong association was found between lymphocytotoxicity inhibition by β2m and the presence of β2m-binding material, suggesting that both assays detected β2m autoantibodies. The presence of β2m antibodies was not dependent on the age or sex of the patients, was not correlated with titers of antinuclear antibodies or rheumatoid factors, and was weakly associated with Clq-binding activity. Inhibition experiments indicated that the amount of β2m required to inhibit lymphocytotoxicity or 125I-β2m binding by SLE sera was much higher than that sufficient to inhibit binding by heterologous sera, suggesting that SLE autoantibodies were of low avidity and might be directed against the β2m determinant(s) accessible in the HLA-β2m complex and at the cell surface.
Evaluation of the Role of IgG Antibodies in Human Natural Cell-Mediated Cytotoxicity Against the Myeloid Cell Line K562
Authors: Kay H. David , Bonnard Guy D. , Herberman Ronald B.
Published: January 2023

The possible role of anti-target cell antibodies in human natural cell-mediated cytotoxicity against the K562 myeloid leukemia cell line was investigated in a 4-hr 51chromium release assay (CRA) by using, as effector cells, peripheral blood lymphocytes from normal, healthy donors. We investigated whether anti-target cell antibodies (IgG) were involved in the mechanism of natural cytotoxicity, either 1) as “arming” antibodies bound to the Fc receptor of the natural killer (NK) cell in vivo, or 2) by synthesis during the in vitro incubation period of the CRA. NK activity was not affected by procedures that were expected to remove cytophilic IgG from effector lymphocytes, such as washing whole, unseparated blood at 37°C three times before exposure to Ficoll-Hypaque; extensive washing (up to ten times) of purified lymphocytes at 37°C; or incubation of lymphocytes at 37°C for as long as 48 hr. After exposure of effector cells to trypsin for 30 min at 37°C, NK activity was always significantly reduced, and was not spontaneously recovered, even after incubation in culture medium for up to 48 hr. NK activity was not restored to trypsinized lymphocytes by incubation with normal autologous or allogeneic sera at 4°C, 24°C, or 37°C for times ranging from 0.5 to 18 hr before the CRA. Further, K562 was not sensitized for ADCC by these same normal sera, in contrast to the strong ADCC, which resulted when the target cells were preincubated with rabbit anti-K562 sera. Only when normal sera were left in the assay for 4 hr did we very occasionally observe boosting of cytotoxicity of untreated or trypsinized lymphocytes. More frequently, sera left in the assay caused some inhibition of cytotoxicity.

When effector cell suspensions were incubated before the CRA, or for the duration of a 4 hr or 18 hr CRA, with various concentrations of potent Fab or F(ab′)2 fragments of goat anti-human F(ab′)2, NK activity was not specifically inhibited. Further, protein A from Staphylococcus aureus, which binds to the Fc portion of most subclasses of human IgG, did not inhibit NK when left in the assay at concentrations up to 100 µg/ml, but significantly inhibited, in a dose-dependent manner, K cell activity to Change cells coated with human anti-HLA serum. Thus, no clear evidence in support of a role for IgG in human NK activity against K562 cells could be demonstrated.
Purification and Biochemical Characterization of Human Lymphocyte Mitogenic Factor (LMF)
Authors: Rutenberg William D. , al-Khalidi Usama , Rosen Fred S. , Merler Ezio
Published: January 2023

Supernatants of human T lymphocytes stimulated by TT antigen release two factors that induce mitogenesis in autologous and allogeneic B lymphocytes. These factors are precipitated by 60% ammonium sulfate and 50% ethanol, and are both destroyed by heating to 70°C for 5 min. By equilibrium ultracentrifugation there was a peak of mitogenic activity in the fraction with a specific gravity of 1.3147 corresponding to a partial specific volume of 0.761. After ultrafiltration through an Amicon XM50 membrane, the concentrate was chromatographed on a Sephadex G-200 column. Mitogenic activity was found only in the post-albumin fraction. When the postalbumin fraction was run on an isoelectrofocusing column, two distinct mitogenic factors were identified. The major peak of mitogenic activity (LMF) had a pI of 6.68 ± 0.05 and the minor peak (MMF) had a pI of 7.27 ± 0.05. Amino acid analysis of LMF identified it as a protein and PAGE showed that LMF probably was a tetramer with a m.w. of 80,000.
Comparison of immune responsiveness in mice after single or multiple donor-specific transfusions.
Authors: Wood M L , Gottschalk R , Monaco A P
Published: January 2023

Immune responsiveness was compared in B6AF1 mice after one, two, three, or four donor-specific DBA/2 blood transfusions (DST). Ten days after the last transfusion, the spleen cells of transfused mice were assayed for direct lymphocyte-mediated cytotoxicity, for the ability to respond in mixed lymphocyte culture (MLC) and cell-mediated lymphocytotoxic (CML) assays to DBA/2 and C3H/He antigens, and for the ability to inhibit the MLC and CML response of normal B6AF1 to DBA/2 and C3H/He antigens. Immune responsiveness was also tested in B6AF1 2 to 80 days after a single DBA/2 DST. The MLC response of transfused mice was specifically suppressed to the blood donor after both single and multiple transfusions. The CML response to DBA/2 was suppressed after a single DST, but returned to normal after multiple transfusions. Spleen cells from transfused mice did not inhibit the MLC response of normal B6AF1 mice to DBA/2 or C3H/He antigens after one or two transfusions regardless of time tested, but were able to inhibit the response to both stimulators after three or more transfusions. The MLC response remained specifically suppressed to the blood donor for as long as 80 days after a single DST, while the CML response was suppressed up to 50 days after transfusion, but had returned to normal by 80 days.
Acute SLE in F1 hybrids between SB/Le and NZW mice; prominently enhanced formation of gp70 immune complexes by a Y chromosome-associated factor from SB/Le mice.
Authors: Izui S , Masuda K , Yoshida H
Published: January 2023

Both sexes of the F1 hybrids between SB/Le and NZW mice developed a spontaneous lupus-like disease. Their disease is essentially identical in time course and nature with autoimmune responses that are seen in the F1 hybrids between BXSB and NZW mice. The presence of abnormal Y chromosomes in the SB/Le strain was proved by the finding that the accelerated disease occurred in the F1 hybrid males only when the male parent was SB/Le but not NZW. The acceleration of disease in male F1 hybrids with abnormal Y chromosome was significantly associated with the enhanced formation of gp70 IC but not anti-DNA antibodies. These results indicate that all or almost all of the genetic abnormalities expressed in the BXSB strain are contributed by the SB/Le strain, and the Y chromosome-associated factor enhances the autoimmune response to serum gp70 antigen more markedly than to DNA antigens.
Regulation of interleukin 2 receptor expression on murine cytotoxic T lymphocyte clones.
Authors: Andrew M E , Braciale V L , Braciale T J
Published: January 2023

We have previously reported that influenza virus-specific cytotoxic T lymphocyte (CTL) clones require antigen and exogenous growth factors for continued proliferation in culture. In this report we show that after stimulation with specific antigen, cloned CTL are capable of limited proliferation in response to interleukin 2 (IL 2) alone but with time these large blast-like cells revert to smaller, quiescent cells that are no longer responsive to IL 2. The IL 2-unresponsive CTL can not be driven to proliferate by supra-optimal concentrations of IL 2, and unresponsiveness correlates with decreased ability to absorb IL 2 from conditioned medium at 0 degrees C, suggesting that unresponsiveness is due to diminished IL 2 receptors. Stimulation of the unresponsive CTL with antigen leads to re-expression of the IL 2 receptor. Decreased absorbing capacity of the unresponsive cells could not be accounted for by their smaller surface area, and the IL 2-unresponsive cells seemed not to down-regulate all their immune functions, as they remained cytotoxic. These results provide a basis for the role of specific antigen in maintaining CTL clones in vitro. Furthermore, these results suggest that antigen-dependent CTL lines can be regulated and that antigen and IL 2 both play a role in their regulation.
Opposite effects of total lymphoid irradiation on T cell-dependent and T cell-independent antibody responses.
Authors: Tanay A , Strober S
Published: January 2023

The effect of total lymphoid irradiation (TLI) on the primary antibody response to the dinitrophenylated heterologous protein, keyhole limpet hemocyanin (DNP-KLH), in complete Freund's adjuvant (CFA), and to the trinitrophenylated polysaccharide antigen, Brucella abortus (TNP-BA), was studied in BALB/c mice. The antibody response to both antigens was diminished in comparison with nonirradiated mice when antigens were injected within 3 days after TLI. When the mice were immunized 30 days after completion of TLI the antibody response to DNP-KLH in CFA was still diminished, but the antibody response to TNP-BA was enhanced 5- to 10-fold as compared with that of control animals. The opposite effect of TLI on the two antibody responses was also observed in a syngeneic primary adoptive transfer system.
Influence of radiation field and fractionation schedule of total lymphoid irradiation (TLI) on the induction of suppressor cells and stable chimerism after bone marrow transplantation in mice.
Authors: Waer M , Ang K K , Van der Schueren E , Vandeputte M
Published: January 2023

When BALB/c mice received 17 daily fractions of 2 Gy each of total lymphoid irradiation (TLI, total dose 34 Gy) and 30 X 10(6) C57 B1 bone marrow cells (BM) on the day after the last fraction, stable bone marrow chimerism without signs of graft-vs-host disease (GVHD) was obtained in 84% of the animals. On the contrary, in BALB/c mice receiving only seven fractions of TLI (total dose 14 Gy), all bone marrow grafts were rejected. When the last two fractions of a 14-Gy TLI course were given without shielding the extra lymphatic tissues (combined total lymphoid + total body irradiation, TLBI), chimerism could be induced in 53% of the animals. When this 14-Gy TLBI schedule was used, it was even possible to administer four fractions per day (multiple fractions per day schedule, MFD), thus reducing the overall treatment time to 2 consecutive days. After this concentrated form of TLBI, chimerism was detected in 35% of the animals. As in the 34-Gy TLI schedule, graft-vs-host reaction could not be prevented in the 14-Gy TLBI schedule when spleen lymphocytes (10 X 10(6) were added to the BM inoculum. Leucopenia or suppression of the phytohaemagglutinin (PHA)-induced blastogenesis could not predict which schedule would result in a successful allogeneic bone marrow take. Suppressor cells of the mixed lymphocyte reaction, on the other hand, were only found in the spleen of BALB/c mice treated with the TLI or TLBI schedules, which also resulted in stable bone marrow chimerism.
FcR epsilon+ lymphocytes and regulation of the IgE antibody system. I. A new class of molecules, termed IgE-induced regulants (EIR), which modulate FcR epsilon expression by lymphocytes.
Authors: Marcelletti J F , Katz D H
Published: January 2023

Exposure of unfractionated murine lymphoid cells to suitable amounts of IgE in vitro results in the de novo expression of Fc receptors for IgE (FcR epsilon) by both T and B lymphocytes. Monoclonal IgE, in the monomeric state, directly induces FcR epsilon expression by B cell-enriched but not T cell-enriched lymphoid cells. In contrast, the same monoclonal IgE in the aggregated state can directly induce FcR epsilon expression by either lymphocyte class independently. The fact that monomeric IgE induces almost equal proportions of FcR epsilon+ B and T cells unfractionated cell cultures, but can directly induce only FcR epsilon+ B cells when lymphocyte subpopulations are independently exposed to IgE, suggested the involvement of either soluble mediators or cognate interactions in this FcR epsilon expression process. Indeed, the studies presented demonstrate that IgE-stimulated lymphoid cells produce soluble mediators, termed IgE-induced regulants (EIR), which can induce FcR epsilon expression in cultures of fresh lymphoid cells. EIR-stimulated FcR epsilon expression is independent of IgE in either its native or processed state, and is largely by T cells of the Lyt-2+ subset. Thus, total depletion of T cells or more selective elimination of the Lyt-2+ subset prevented the development of FcR epsilon+ cells in cultures exposed to EIR but not in those exposed to monomeric IgE. Conversely, depletion of B cells had the opposite effect in that the remaining T cells retained the ability to express FcR epsilon in response to EIR but were unresponsive to monomeric IgE. Because of its selective activity in inducing FcR epsilon expression by T lymphocytes, EIR from unfractionated lymphoid cell cultures has been designated EIRT. This selectivity of EIRT inductive properties for T lymphocytes was additionally confirmed by analyses of the FcR epsilon+ lymphoid cells subsequent to induction with IgE or EIRT. Thus, unlike monomeric IgE, which induces FcR epsilon+ cells equally distributed among T and B lymphocytes, EIRT induces FcR epsilon+ cells in only the T cell class. These findings indicate that production of the EIRT and subsequent expression of FcR epsilon by Lyt-2+ T cells depends upon the initial interaction of IgE with B cells. Finally, an interesting paradox observed was that although IgE-induced FcR epsilon expression by B cells is unaffected by total T cell depletion, selective blocking of just Lyt-1+ T cells significantly diminishes this FcR epsilon induction process.(ABSTRACT TRUNCATED AT 400 WORDS)
FcR epsilon+ lymphocytes and regulation of the IgE antibody system. IV. Delineation of target cells and mechanisms of action of SFA and EFA in inhibiting in vitro induction of FcR epsilon expression.
Authors: Marcelletti J F , Katz D H
Published: January 2023

SFA and EFA are derived from distinct mouse T cell hybridomas secreting one or the other (but not both) factor, and although both are capable of inhibiting FcR epsilon expression by unfractionated spleen cells induced by monomeric IgE, neither was inhibitory for EIRT-induced FcR epsilon expression by T cells in the same cell population. This suggests that the final target cell for the inhibitory effects of SFA and EFA is the FcR epsilon+ B lymphocyte. T cells are required for both SFA- and EFA-mediated FcR epsilon inhibition, and more precisely, as shown in this study, SFA stimulates Lyt-1+ cells in the presence or absence of IgE to produce a suppressive effector molecule (SEM), and EFA together with IgE stimulates Lyt-2+ cells to produce an enhancing effector molecule (EEM), both of which can directly inhibit FcR epsilon expression by B cells. SFA and SEM can inhibit both IgE- and EIRB-induced FcR epsilon expression by B cells, indicating that SFA may act by blocking the EIRB-mediated expansion of the FcR epsilon+ B cell population. EFA and EEM, in contrast, can inhibit IgE-induced but not EIRB-induced FcR epsilon expression, indicating that EFA may act at some point before the release of EIR, perhaps involving those FcR epsilon+ B cells that respond to IgE and produce EIRB. Finally, although neither SFA and EFA display IgE binding properties, both SEM and EEM, in contrast, are IgE binding factors (IgE-BF) and may be homologous to the suppressive IgE binding factor and potentiating IgE binding factor described by other investigators. The possible interrelationships between these various cells and factors are discussed.
The role of class I MHC products in polyclonal activation of CTL function.
Authors: Kane K , Clark W R
Published: January 2023

The generation of CTL function by agents such as lectins, oxidative chemicals, or serum components has been regarded as independent of class I MHC products, because the CTL thus generated are able to lyse virtually any allogeneic target. However, we show here that CTL activation by lectin requires interaction of the pre-CTL with a class I MHC product on the lectin-presenting cell. The lectin-presenting cell can be an irradiated syngeneic or allogeneic spleen cell or, alternatively, lectin can be seen on a neighboring pre-CTL. In either case, there is an absolute requirement for simultaneous (although probably unlinked) perception of a class I MHC product. These results suggest that restricted clonal CTL activation by antigen, and polyclonal activation by so-called "nonspecific" mitogenic agents, may proceed through similar if not identical pathways.
T cell subsets in (responder x nonresponder)F1 mice regulating antibody responses to L-glutamic acid60-L-alanine30-L-tyrosine (GAT).
Authors: Pierce C W , Kapp J A , Sorensen C M , Trial J
Published: January 2023

Immune responses to GAT are controlled by H-2-linked Ir genes; soluble GAT stimulates antibody responses in responder mice (H-2b) but not in nonresponder mice (H-2q). In nonresponder mice, soluble GAT stimulates suppressor T cells that preempt function of helper T cells. After immunization with soluble GAT, spleen cells from (responder x nonresponder: H-2b X H-2q)F1 mice develop antibody responses to responder H-2b GAT-M phi but not to nonresponder H-2q GAT-M phi. This failure of immune F1 spleen cells to respond is due to an active suppressor T cell mechanism that is activated by H-2q, but not H-2b, GAT-M phi and involves two regulatory T cell subsets. Suppressor-inducer T cells are immune radiosensitive Lyt-1 +2-, I-A-, I-J+, Qa-1+ cells. Suppressor-effector T cells can be derived from virgin or immune spleens and are radiosensitive Lyt-1-2+, I-A-, I-J+, Qa-1+ cells. This suppressor mechanism can suppress responses of virgin or immune F1 helper T cells and B cells. Helper T cells specific for H-2b GAT-M phi are easily detected in F1 mice after immunization with soluble GAT; helper T cells specific for H-2q GAT-M phi are demonstrated after elimination of the suppressor-inducer and -effector cells. These helper T cells are radioresistant Lyt-1+2-, I-A+, I-J-, Qa-1- cells. These data indicate that the Ir gene defect in responses to GAT is not due to a failure of nonresponder M phi to present GAT and most likely is not due to a defective T cell repertoire, because the relevant helper T cells are primed in F1 mice by soluble GAT and can be demonstrated when suppressor cells are removed. These data are discussed in the context of mechanisms for expression of Ir gene function in responses to GAT, especially the balance between stimulation of helper vs suppressor T cells.
Regulation of immune responses via genetically-restricted cellular interactions. I. Augmentation of antibody responses by idiotype-specific enhancing B lymphocytes.
Authors: Yamamoto H , Bitoh S , Fujimoto S
Published: January 2023

We previously reported that B lymphocytes obtained from BALB/c mice that had been immunized with M104E myeloma protein have an idiotype-specific enhancing activity for anti-dextran B1355S antibody responses in vivo. The enhancing cells were Thy-1-, Lyt-1-,2-, nylon wool-adherent and rabbit anti-mouse immunoglobulin (RAMG) dish adherent. The in vitro analysis described in this report also revealed that the enhancing cells had a B cell phenotype and were specifically enriched in M104E or J558 myeloma protein-coated dishes but not by irrelevant monoclonal antibodies. The significance of these B-B cell interactions were analyzed in vitro by using various Igh-1 and H-2 congeneic strains of mice. The idiotype immune B lymphocytes obtained from BALB/c and BAB-14 could enhance the antidextran antibody responses of BALB/c B lymphocytes in an idiotype-specific manner. On the other hand, C.AL-20 and CB-20 strains could not induce the idiotype-specific enhancing B cell activity in dextran-immune BALB/c B cells. These results suggest that the capability of enhancing B cell induction is related to the producibility of the respective idiotype in that strain of mice. Moreover, the B cells obtained from BALB/c mice immune to the idiotype cooperated well with the dextran-immune B cells of BALB/c but not of BALB.K and vice versa. These results indicate that successful cooperation between those two types of B lymphocytes requires the same MHC haplotype. The roles of these genetically restricted cellular interactions in the immune system are discussed.
The interference of T cell activation by calcium channel blocking agents.
Authors: Birx D L , Berger M , Fleisher T A
Published: January 2023

Calcium has been identified as having an important role as a transmembrane messenger in the activation signal for lymphocytes. To additionally examine this model, we evaluated the effect of calcium channel blocking drugs (verapamil, nifedipine, and diltiazem) on lymphocyte activation. In these studies we found that the drugs inhibit, in a dose-dependent fashion, the proliferation of T cells and the appearance of certain activation antigens after mitogen stimulation. This appears to result from the marked decrease in mitogen-induced 45calcium (45Ca+2) influx secondary to the addition of these agents. In addition, T cell proliferation resulting from IL 2 binding to its receptor is also suppressed by the calcium channel blocking drugs. These data suggest that the passive calcium channel plays a pivotal role in both the initial activation of T cells after ligand-receptor interaction and the ongoing signal for proliferation provided by IL 2 binding to its receptor.
Mechanism of 8-mercaptoguanosine-mediated adjuvanticity: roles of clonal expansion and cellular recruitment.
Authors: Goodman M G , Weigle W O
Published: January 2023

The mechanism by which increased numbers of antigen-responsive B cells are generated in the presence of antigen and the C8-substituted guanine ribonucleoside, 8-mercaptoguanosine (8MGuo), has been investigated. Augmentation of the primary humoral response of splenocytes to antigen cannot be ascribed to the additive effects of the underlying antigen-specific response and the nonspecific (polyclonal) response induced by 8MGuo. This is clear from a consideration of the magnitude of the responses involved, as well as from a murine model (the SJL mouse) that does not generate a nonspecific response to the substituted nucleoside but responds to it with the usual degree of immunoenhancement in the presence of antigen. Other approaches suggest that two mechanisms are involved in adjuvanticity, one whereby preexisting antigen-specific B cells undergo clonal expansion, and one in which cells not normally participating in the response are recruited in the absence of clonal expansion. The latter mechanism appears to be the dominant one insofar as models in which 8MGuo-induced proliferation fails to occur (such as after irradiation, or in the SJL mouse) nonetheless exhibit strong adjuvant effects. Analysis of precursor frequency of antigen-specific B cells indicates that for each mature, antigen-responsive B cell present in adult murine spleen, an average of four additional cells can be recruited by the conjoint actions of antigen and 8MGuo. One group subject to such recruitment is the immature antigen-specific B cell, whose degree of functional maturity is accelerated in the presence of antigen and 8MGuo.
Differential effects of two anti-apo-cytochrome c-specific monoclonal antibodies on the function of apo-cytochrome c-specific murine T cell clones.
Authors: Corradin G , Juillerat M A , Engers H D
Published: January 2023

A murine monoclonal antibody (SJL 2-4) specific for the antigen apo-cytochrome c was shown to inhibit both antigen-induced proliferation and lymphokine secretion by an apo-cytochrome c-specific BALB/c helper T cell clone. The inhibition was specific because additional apo-cytochrome c-specific T cell clones were not inhibited by the same monoclonal antibody. Time course studies of the inhibition indicated that the initial 8 hr of contact between T cell clones and antigen-presenting cells were critical for activation of the T cell clones. Inhibition of T cell functions by antigen-specific antibodies appeared to correlate with the antibody-antigen binding constant because a second monoclonal antibody (Cyt-1-59), with identical specificity but with a lower affinity constant for apo-cytochrome c, had very little inhibitory effect on the proliferation or lymphokine secretion of apo-cytochrome c-specific T cell clones.
T cell repopulation from functionally restricted splenic progenitors: 10,000-fold expansion documented by using limiting dilution analyses.
Authors: Miller R A , Stutman O
Published: January 2023

Mice depleted of T cells by thymectomy, lethal irradiation, and reconstitution with Thy-1-depleted syngeneic bone marrow were given graded doses of splenic T cells to see whether post-thymic cells had the ability to regenerate immune function in these hosts. Using limiting dilution methods to estimate the number of antigen- and mitogen-responsive cells in recipients 12 to 20 wk after reconstitution, we found that new helper and cytotoxic precursor cells were produced, but attained levels only 10 to 20% of normal. Because these repopulated mice were able to produce nearly normal levels of helper and cytotoxic activity in conventional, high density cultures, despite their relative paucity of precursors, we infer that their normal function in conventional assays may reflect a balanced deficiency of effector and regulatory cell types. Surface phenotyping of the progenitor cells responsible for repopulation showed that Lyt-2- cells were required for helper cell regeneration and that Lyt-2+ cells acted as progenitors only for the cytotoxic lineage, contrary to earlier speculation that the splenic Lyt-1+ 2+ (Ly-123) pool included cells antecedent to both effector lineages. Comparison of the number of injected progenitors needed to produce repopulation with the number of new precursor cells eventually produced suggests that the relevant progenitors are able to undergo 10,000-fold expansion in 12 to 20 wk. Numerical expansion in the periphery from thymic-processed cells could well be a major source of new lymphocytes in adult mice.