bluuebunny/crossref_metadata_2025 huggingface dataset:
The nature of the interaction between suppressor and helper T cells in the response to LDHB.
Authors: Baxevanis C N , Nagy Z A , Klein J
Published: December 2022

Purified Lyt-1+2+ T cells were depleted of alloreactive cells by BUdR and light treatment, and then were primed in vitro against LDHB presented on allogeneic APC. Such cells could be restimulated by LDHB on the same allogeneic APC, but not by LDHB on APC syngeneic with the T cells. The restimulated T cells suppressed the proliferative response of Lyt-1+2- T cells primed and restimulated by the same antigen. The suppression, which was antigen specific, occurred after a 6-hr co-culture of the suppressor (Tse) and proliferating helper (Th) cells. The successful interaction (as measured by suppression) between allogeneic Th and Tse cells was found to be determined by the restriction specificity but not the MHC haplotype of Th cells, and the MHC haplotype but not the restriction specificity of Tse cells. Thus, suppression occurred only when the Tse cells carried genes controlling the MHC molecules that served as restriction elements for antigen recognition by the Th cells. No evidence could be obtained for the participation of APC in the Tse-Th interaction. The data suggest the interaction is based on the recognition by the Th cell of the antigen presented in the context of MHC molecules controlled by the Tse cell.
Natural killer (NK) cell activity during lymphatic regeneration: early appearance of Thy-1+ NK cells and highly interleukin 2-(IL 2) receptive, Thy-1- cells.
Authors: Hurme M , Sihvola M
Published: December 2022

The appearance of natural killer (NK) cells, i.e., cells that can lyse tumor-derived target cells without intentional immunization, was studied during regeneration after a sublethal dose (300 mg/kg) of cyclophosphamide (Cy). It was found that NK activity started to increase in parallel with the number of cells in the spleen, reaching normal levels 8 to 9 days after Cy injection. The early appearing NK cells differed, however, from the NK cells of the normal spleen; all the activity was abolished by treatment with a monoclonal anti-Thy-1 antibody plus complement (C). The early regenerating population contained cells that could given rise in vitro, in the presence of interleukin 2 (IL 2), to higher amounts of NK-active cells than cells of a normal spleen. Pretreatment with anti-Thy-1 (plus C) did not inhibit the formation of these in vitro NK-active cells, indicating that they were not derived from these Thy-1+ NK cells. The NK cells formed in vitro expressed both the asialo GM1 and the Thy-1 antigens. These data suggest that i) the expression of the Thy-1 antigen on NK cells is connected to their stage of maturation or to the rate of proliferation, and ii) the precursors for the in vitro activated NK cells are not NK-active cells themselves.
Binding of cyclosporine by human lymphocytes and phospholipid vesicles.
Authors: LeGrue S J , Friedman A W , Kahan B D
Published: December 2022

The purpose of this investigation was to identify and characterize a possible plasma membrane receptor for cyclosporine (CsA) on human lymphoid cells. Binding of 3H-CsA by normal human lymphocytes and purified lymphoid subpopulations was examined using ligand concentrations ranging from 5 X 10(-7) to 10(-10) M. Specificity was determined using a 500-fold excess of unlabeled drug. No differences were observed in the uptake of 3H-CsA by B cells or T cells using Cartesian or semilogarithmic analyses. Scatchard analysis of the specific binding of CsA by normal peripheral blood lymphocytes yielded two dissociation constants: a high affinity site with a KD of 2 to 6 X 10(-9) M and a low affinity site with a KD of about 10(-7) M CsA. Scatchard analysis of specific CsA uptake by purified splenic T cells and B cells showed both populations to exhibit a low affinity site (KD = 3 to 6 X 10(-7) M and 5 to 8 X 10(-7) M, respectively), whereas only B cells bore a high affinity site (KD = 2 X 10(-9) M). Analysis of specific CsA uptake by cultured human kidney cells and phospholipid vesicles (1:1 molar ratio of phosphatidylcholine:cholesterol) showed both these targets to display a single, low affinity binding site (KD = 1 X 10(-7) M and 2 X 10(-8) M, respectively). The relevance of the low affinity site to CsA-mediated in vitro immunosuppression was suggested by the need for 10(-7) M CsA to achieve 50% suppression of lymphoproliferation during mixed lymphocyte culture. Taken together, these data argue against the existence of a specific CsA receptor on the surface of human T cells. Although a role for the high affinity B cell receptor in some types of CsA-induced immunomodulation cannot be excluded, the present study suggests that immunosuppression is achieved by the partitioning of the hydrophobic CsA molecule into the membrane lipid bilayer, thereby perturbing homeostatic control of membrane function.
The instructor cell for the human procoagulant monocyte response to bacterial lipopolysaccharide is a Leu-3a+ T cell by fluorescence-activated cell sorting.
Authors: Helin H J , Fox R I , Edgington T S
Published: December 2022

A variety of responses of cells of the lymphoid system are associated with acquisition of the capacity to initiate the coagulation protease pathways. The initiating or procoagulant molecules are produced by the monocyte; however, a number of studies have indicated that lymphocyte collaboration is required. The induction of human monocyte procoagulant activity (PCA) by the model stimulus bacterial lipopolysaccharide (LPS) was examined in the present study by using relatively highly purified monocyte and lymphocyte populations in reconstitution experiments. Consistent with prior studies, the PCA response could not be generated by highly purified monocytes alone after exposure to LPS. The ability to generate PCA was restored to these monocyte populations by the addition of fibronectin-gelatin nonadherent lymphocytes, nylon wool effluent T cells, or Leu-3a+ inducer/helper T cells selected by fluorescence-activated cell sorting. T cells added to monocytes at a ratio of 8:1 or higher, and Leu-3a+ cells added at a ratio of 6:1 or higher, provided a maximal collaboration for monocyte PCA induction by LPS. These results substantiate further previous suggestions of an absolute requirement for collaborating T cells and demonstrate that these instructor cells carry a marker for the inducer/helper subset.
Analysis of the defects responsible for the impaired regulation of EBV-induced B cell proliferation by rheumatoid arthritis lymphocytes. II. Role of monocytes and the increased sensitivity of rheumatoid arthritis lymphocytes to prostaglandin E.
Authors: Hasler F , Bluestein H G , Zvaifler N J , Epstein L B
Published: December 2022

Diminished regulation of EBV-induced B cell proliferation by T cells from patients with rheumatoid arthritis (RA) is paralleled by diminished production of gamma-interferon in response to autologous but not allogeneic stimulation. We have shown that the adherent cell subpopulation within the autologous RA stimulators plays a major role in the RA defect. In analyzing the mechanisms responsible for the adherent cell effect in RA, we examined the contribution of prostaglandin production. Indomethacin treatment (1 microgram/ml) of the RA auto-MLR led to increased production of supernatant inhibitory activity (8% +/- 4 without, 57% +/- 4 with indomethacin), but had no significant effect on the inhibition of EBV-induced B cell proliferation by normal auto-MLR supernatants. Adding excess autologous adherent cells to the normal auto-MLR, however, led to an indomethacin-reversible decline in the production of the inhibitory factor without suppressing the auto-MLR proliferative response. The adherent cell effect could be reproduced by adding PGE1 or PGE2 (10(-8) to 10(-6) M) to the normal auto-MLR. PGE2 levels in 72-hr auto-MLR supernatants were similar in RA (4.2 +/- 1 ng) and normal control (3.6 +/- 0.5 ng/ml) supernatants. Because we could not detect differences in PGE production, we assessed the sensitivity of adherent cell-depleted normal and RA auto-MLR to exogenous PGE. Concentrations of 10(-7) to 10(-6) M PGE were needed to block production of the inhibitory factor by to normal cells, whereas only 10(-13) to 10(-12) M PGE1 completely blocked it in RA cell cultures. Thus, the defective production of gamma-interferon in the RA auto-MLR is, at least in part, due to enhanced sensitivity of the RA lymphocytes to adherent cell-produced prostaglandins.
Chemotactic properties of partially purified human epidermal cell-derived thymocyte-activating factor (ETAF) for polymorphonuclear and mononuclear cells.
Authors: Luger T A , Charon J A , Colot M , Micksche M , Oppenheim J J
Published: December 2022

Human epidermal cell thymocyte-activating factor (ETAF) derived from either normal epidermal cells or a squamous cell carcinoma cell line has recently been shown to be a low m.w. protein that is indistinguishable from human macrophage-derived interleukin 1 (IL 1). As with human IL 1, human ETAF elutes from Sephadex S-200 gel in two major peaks at m.w. 70,000 to 40,000 and m.w. 25,000 to 12,000. Rechromatography of the higher m.w. fraction of ETAF yielded some of the lower m.w. activity, and chromatofocusing of high m.w. ETAF yielded the same three isoelectric points as the lower m.w. ETAF. Partially purified human ETAF as well as IL 1 were chemotactic for polymorphonuclear and mononuclear leukocytes. In addition, exposure of PMN to ETAF stimulated increased metabolic activity as demonstrated by greater reduction of intracellular nitroblue tetrazolium. Therefore, this study lends further support for an important role of ETAF in the pathogenesis of inflammatory skin diseases.
The thymic differentiation markers T6 and M241 are two unusual MHC class I antigens.
Authors: van de Rijn M , Lerch P G , Knowles R W , Terhorst C
Published: December 2022

The human beta 2-microglobulin (beta-2m)-associated human thymocyte differentiation antigens T6 and M241 were compared using biochemical techniques. T6 and M241 antigens reside on different molecules with apparent m.w. of 49,000 and 43,000, respectively. Here we show that both proteins have a protein backbone m.w. of 33,000. In addition, T6 and M241 have a large portion of their peptides in common. When we compared the protein backbone m.w. of T6 and M241 with the murine beta-2m-associated thymus leukemia (TL) antigens, we found a considerable difference in size, suggesting that T6 and M241 may not be human homologues of TL antigens and constitute a novel type of major histocompatibility (MHC) class I antigens.
Diverse specificities of five monoclonal antibodies reactive with glycophorin A of human erythrocytes.
Authors: Ochiai Y , Furthmayr H , Marcus D M
Published: December 2022

Glycophorin A (GPA), the major sialoglycoprotein of human red cells, bears blood group MN determinants, and is a useful marker of the erythroid lineage in differentiating cells. Five monoclonal antibodies that react with GPA and possess a spectrum of serologic properties and fine specificities were obtained by immunization of mice with umbilical cord erythrocytes. Three antibodies, B22A, D22 and E11B, did not agglutinate En(a-) erythrocytes, genetic variants that lack GPA, and F11 and J11A agglutinated these cells very weakly. Antibodies B22A, E11B, and F11 agglutinated protease-treated cells more strongly than untreated erythrocytes, and they appeared to react with a peptide determinant located on the C-terminal side of the site at which trypsin cleaves GPA in the intact erythrocyte. In contrast to B22A and E11B, the hemagglutinating activity of F11 was not inhibited by purified GPA, nor did it bind to GPA in a solid phase immunoassay, but it immunoprecipitated GPA. Antibodies D22 and J11A appeared to be directed against carbohydrate determinants, or conformational determinants created by hydrogen bonding or electrostatic interactions between carbohydrate and protein. A preferential reaction of antibody J11A with MM over NN GPA was demonstrated by its reactions with enzyme-treated erythrocytes, its inhibition by purified GPA or its tryptic fragments, and by an ELISA assay.
The relationship between immune interferon production and proliferation in antigen-specific, MHC-restricted T cell lines and clones.
Authors: Hecht T T , Longo D L , Matis L A
Published: December 2022

The release of immune or gamma interferon (IFN-gamma) by major histocompatibility complex (MHC)-restricted pigeon cytochrome c-specific Lyt 1+2-, interleukin 2 (IL 2)-producing proliferative T cell clones when cultured with antigen and antigen-presenting cells (APC) is a sensitive measure of the state of activation of the cell. In general, the fine specificity of T cell activation was similar when activation was measured either by IFN-gamma production or by proliferation. In response to antigen and the correct Ia molecule, the T cell clones produced both high titered IFN-gamma and a strong proliferative response. However, IFN-gamma production and the degree of proliferation of the T cell clones differed at high antigen concentrations. As antigen concentration increased, the magnitude of proliferation became submaximal whereas the IFN-gamma response became maximal suggesting that IFN-gamma produced by the cells might act as an autoregulatory molecule inhibiting the proliferative response. Stimulating the T cell to divide via its IL 2 receptor by adding exogenous IL 2 produced high levels of proliferation but only low titers of IFN-gamma activity. In addition, irradiation of the clone eliminated the IFN-gamma release induced by IL 2 but did not affect the IFN-gamma release induced by antigen and Ia. Thus proliferation is not essential for IFN-gamma production and unlike antigen and Ia, IL 2 functions predominantly as a proliferative signal and not as a signal for factor release. Two T cell clones showed a dissociation of IFN-gamma production and proliferation. In one case, a clone that proliferated in response to both allogeneic and antigenic stimuli released IFN-gamma in response to antigen but failed to produce IFN-gamma in response to the allogeneic stimulus. A second clone that showed a strong proliferative response to pigeon cytochrome c but no proliferative response to a species variant of cytochrome c, tobacco hornworm moth (THWM) cytochrome c, produced IFN-gamma when stimulated with either of these antigens. Thus, the sensitivity of detecting activation of T cell clones as measured by the release of an individual lymphokine varies from one clone to another.
Modulation of the biologic activities of IgE-binding factors. III. Switching of a T cell hybrid clone from the formation of IgE-suppressive factor to the formation of IgE-potentiating factor.
Authors: Huff T F , Uede T , Iwata M , Ishizaka K
Published: December 2022

Incubation of rat-mouse T cell hybridoma cells, 23B6, with rat immunoglobulin E (IgE) results in the formation of the 15,000-dalton IgE-suppressive factor and the 30,000-dalton IgE-binding factor, which has neither potentiating activity nor suppressive activity on the IgE response. Another T cell hybridoma, 23A4 cells, produces the 30,000-dalton "inactive" IgE-binding factor upon incubation with IgE. Both the 15,000-dalton IgE-suppressive factor and the 30,000-dalton IgE-binding factor lacked affinity for lentil lectin but bound to peanut agglutinin. When the 23B6 cells were incubated with IgE in the presence of lysolecithin, the majority of the 15,000-dalton IgE-binding factor formed by the cells gained affinity for lentil lectin, and this factor selectively potentiated the IgE response. The glycosylation-enhancing factor, which was formed by stimulation of normal spleen cells with lymphocytosis-promoting factor (LPF or pertussigen), also switched 23B6 cells from the formation of IgE-suppressive factor to the formation of IgE-potentiating factor. It was also found that the 30,000-dalton "inactive" IgE-binding factor, formed by both 23B6 and 23A4 cells, gained the ability to potentiate the IgE response, when the cells were cultured with IgE in the presence of glycosylation-enhancing factor. The results indicate that IgE-potentiating factor and IgE-suppressive factor share common precursors, and that biologic activities of IgE-binding factors are decided by their carbohydrate moieties. Incubation of the two hybridoma cells with lysolecithin or glycosylation-enhancing factor results in an increase in the proportion of FC epsilon R+ cells, suggesting that the assembly of N-linked oligosaccharide to precursor molecules is intrinsic for the expression of FC epsilon R.
In vitro analysis of the cellular interactions between unprimed lymphocytes responsible for determining the class of response an antigen induces: specific T cells switch a cell-mediated response to a humoral response.
Authors: Bretscher P A
Published: December 2022

Unprimed murine spleen cells, when cultured at different densities but in the presence of the same concentration of antigen, are induced to mount different classes of response. Three modes of behavior are found. A low density does not support the induction of any response, a medium density supports a transient IgM and substantial delayed-type hypersensitivity (DTH) response, and a high density only supports a sustained IgM response. This in vitro system has been used to show that a low density of cells, when complemented with irradiated specific T cells, can mount a DTH response, and thus behave as a medium density of cells. These observations show that the induction of DTH requires helper T cells, and that a medium density, in contrast to a low density, allows sufficient collaboration to obtain a DTH response. The observation that a high density only mounts a sustained humoral response suggests that the formation of more helper T cell-dependent signals than the number generated at a medium density may be required to induce a sustained humoral response as well as the suppression of DTH. This hypothesis is supported by the findings that the response by a medium density of cells is dramatically affected by the addition of irradiated antigen-specific helper T cells; the DTH response is specifically suppressed and a sustained humoral response is observed. These results show that the induction of a humoral response is more T cell dependent than the induction of a cell-mediated response and provides an in vitro means for switching a cell-mediated response to a humoral one in an antigen-specific manner. Observations are also presented to show that the production of antibody by a high density of cells is not a prerequisite for the suppression of DTH reactivity.
A study of the functional capabilities of human neonatal lymphocytes for in vitro specific antibody production.
Authors: Yarchoan R , Nelson D L
Published: December 2022

The ability of neonatal B and T cells to participate in the in vitro production of anti-influenza virus antibody was studied. Peripheral blood mononuclear cells from nearly all normal adults produce anti-influenza virus antibody when stimulated in vitro with type A influenza virus. Cord blood mononuclear cells, however, consistently failed to do so. Using Epstein-Barr virus activation or coculture with irradiated adult T cells in the presence of influenza virus to identify precursor B cells for anti-viral antibody production, newborns were found to have a decreased number of influenza-specific B cells as compared with adults. Thus, a paucity of precursor B cells for anti-influenza virus antibody was one factor contributing to the absent in vitro antibody response. Additional studies were undertaken to investigate the capabilities of newborn T cells in the in vitro response to influenza virus. Newborn T cells failed to proliferate when cultured with influenza virus. Irradiated newborn T cells were, however, able to provide help for specific antibody production in influenza virus-stimulated cocultures with allogeneic adult B cells, and newborn T cells proliferated when stimulated with alloantigens; their helper function in allogeneic coculture was, thus, likely mediated by T cells stimulated by alloantigens rather than by influenza virus. In the absence of T cell irradiation, no antibody was produced in cocultures of adult B cells and neonatal T cells, at least in part as the result of a radiosensitive suppressor T cell. Suppression in influenza virus-stimulated allogeneic cocultures was also observed with normal adult T cells and is, therefore, a property of both newborn and adult T cells. Thus, allogeneic help and suppression can both be manifested in exogenous antigen-stimulated allogeneic cocultures. In addition, both of these allogeneic effects can be mediated by neonatal T cells, indicating that these functions are present at the time of birth and do not require previous exogenous antigenic exposure for expression.
Analyses of the serum concentrations and antigenic determinants of thyroglobulin in chickens susceptible to autoimmune thyroiditis.
Authors: Sanker A J , Sundick R S , Brown T R
Published: December 2022

These studies revealed an abnormal elevation in serum thyroglobulin (Tg) concentrations of the thyroiditis-prone OS chicks. Their serum levels, measured by a sensitive and specific RIA, remained high for the first 2 wk of age, a time preceding significant lymphoid infiltration of their thyroid glands. The elevated serum Tg levels probably resulted from, or were related to, hyperactivity of the OS thyroid gland. Reducing the activity of the OS thyroid gland by exogenous administration of T4 caused a temporary but significant reduction in thyroidal infiltration and the synthesis of Tg antibodies. In addition to the analysis of serum concentrations of Tg, a competitive binding RIA was developed to determine whether unique antigenic determinants exist on Tg isolated from OS thyroid glands. This was proved to be unlikely because OS chicks produced autoantibodies that fully cross-reacted with Tg isolated from normal chicken thyroid glands. The relationships between intrinsic thyroid hyperactivity, high serum Tg levels, the sensitization of OS thymocytes, and thyroiditis are discussed.
Constitutive production by the WEHI-3 cell line of B cell growth and differentiation factor that co-purifies with interleukin 1.
Authors: Booth R J , Prestidge R L , Watson J D
Published: December 2022

The myelomonocytic cell line WEHI-3 produces constitutively a factor that affects the growth and differentiation of murine B cells in culture. This cell line also secretes colony-stimulating factors (CSF), interleukin 1 (IL 1) but not interleukin 2. Sequential purification through AcA54 gel filtration, DEAE-Sephacel ion exchange chromatography, and buffer electrofocussing clearly resolved the B cell growth and differentiation factor (BGDF) from the CSF activities but failed to separate BGDF from IL 1. The WEHI-3-derived material responsible for BGDF/IL 1 activity, however, exhibited different behavior on DEAE chromatography (elution at 175 mM NaCl) to that reported for IL 1 from the P388D1 cell line (elution at 50 mM NaCl). B cell growth and differentiation could be induced by WEHI-3 BGDF/IL 1 in cultures of normal spleen cells depleted of T cells and adherent cells but not in cultures of spleen cells from B cell-deficient CBA/N mice, even though thymocytes from such mice displayed a normal response to IL 1. Significant B cell proliferation induced by BGDF/IL 1 was apparent only in the presence of submitogenic concentrations of anti-mouse IgM antibodies, but under these conditions few antibody-forming cells (AFC) were generated. In contrast, B cell differentiation to AFC occurred in the presence of the factor alone, and this response was inhibited by anti-IgM. Thus there appeared to be a reciprocal relationship between B cell proliferation and differentiation induced by BGDF/IL 1. The significance of these results is discussed in the light of other recent studies of BGDF.
Recognition of HLA-A2 mutant and variant target cells by an HLA-A2 allospecific human cytotoxic T lymphocyte line.
Authors: Ware C F , Krangel M S , Pious D , Burakoff S J , Strominger J L
Published: December 2022

HLA-A2 specific human cytotoxic T lymphocytes (CTL) cell lines have been developed using T cell growth factor and coculture of peripheral blood lymphocytes with selected allogeneic target cell lines. The CTL-8 line showed specificity for human leukocyte antigens (HLA)-A2 bearing target cells after 5 weeks in culture when tested against a panel of 14 lymphoblastoid cell lines in a 51Chromium (51Cr) release assay. Purified anti-human leukocyte antigens (HLA) monoclonal antibodies W6/32 and PA2.1 inhibited cytolysis by 85% and 60%, respectively. The CTL-8 line lysed non-HLA-A2 target cells in the presence of lectins concanavalin A (Con A) or phytohemagglutinin-P lectin (PHA-P) indicating the specificity of cytolysis was not due to nonspecific resistance of target cells to the CTL-lytic mechanism. The T5-1 HLA-A2 mutant cell series were tested as targets for the CTL-8 line. Cell clones 8.18.1, 8.21.1 and 8.6.1, which express altered HLA-A2 molecules as determined by their decreased reactivity with allospecific monoclonal antibodies, were lysed by the CTL-8 line as efficiently as the T5-1 wild type. These cell lines also acted as efficient cold target competitors for a normal HLA-A2 target cell. The 8.14.1 cell clone expressed a lower amount of HLA-A2 alloantigen and showed a corresponding decreased reactivity with CTL-8 in direct cytolytic and cold target competitive inhibition assays. In contrast, the M7 and DK1 HLA-A2 variant cell lines, which express normal HLA-A2 serological determinants, were inefficiently lysed by CTL-8 and did not act as competitive inhibitors of normal HLA-A2 target cells. These results support the concept that the alloantigenic determinant(s) recognized by T cells and antibodies occur at separate regions on the HLA-A2 molecule.
Changes in cell-surface expression of MHC and Thy-1.2 determinants following treatment with lipid modulating agents.
Authors: Muller C P , Stephany D A , Shinitzky M , Wunderlich J R
Published: December 2022

Treatment of normal mouse spleen cells with lipid fluidity modulators changes the expression of cell-surface H-2 determinants. BALB/c spleen cells treated for 1 to 2 hr with cholesteryl hemisuccinate (CHS) displayed reduced levels of all tested H-2 determinants (H-2L, H-2K, and H-2D) as evaluated by flow microfluorometry and increased membrane lipid packing density as determined by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence polarization. In contrast, decreasing membrane lipid packing density by phosphatidylcholine treatment decreased DPH fluorescence polarization and increased the expression of MHC determinants. The effects were selective in that expression of Thy-1.2 determinants was decreased by the latter treatment and not increased by CHS. The results are discussed in terms of passive modulation of antigenic expression.
Analysis of the anti-alpha 1 leads to 3 dextran response with monoclonal anti-idiotype antibodies.
Authors: Stohrer R , Lee M C , Kearney J F
Published: December 2022

The antibody response to alpha 1 leads to 3 dextran (DEX) in BALB/c mice consists of a family of closely related yet highly heterogeneous molecules. Although these antibodies have been previously characterized both idiotypically and structurally, detailed analysis of responding clones has not been possible using conventional anti-idiotype antibodies. Monoclonal syngeneic and allogeneic anti-idiotype antibodies (MAIDs) specific for anti-DEX antibodies were used in this study to dissect the serum antibody response to DEX in BALB/c mice. The constructed MAIDs showed considerable heterogeneity by isoelectric focusing and by their binding characteristics to a series of DEX specific myeloma and hybridoma proteins. The predominant heavy chain isotype of these MAIDs was gamma 1. These antibodies were used to identify individual idiotypic structures (IdI) on J558, or M104E as well as cross-reactive determinants common to both (IdX). Although both IdX and IdI MAIDs were obtained, IdI specific antibodies were obtained more frequently. BALB/c mice immunized with DEX produced antibodies expressing both IdI but in highly variable amounts. A large percentage of, but not all DEX specific antibody, could be accounted for by IdX bearing antibodies. Suppression of adult and neonatal mice by IdI specific MAIDs was effective with precise elimination of only those clones expressing IdI determinants leaving the total lambda bearing anti-DEX response intact. Suppression of adults and neonates by an IdX specific MAID resulted in a temporary and partial suppression of the total lambda bearing anti-DEX response along with total suppression of the IdX portion of the response. Unlike other systems these monoclonal antibodies produce only suppression, and under a variety of conditions enhancement of anti-DEX responses has not been observed.
Murine thymocyte and splenocyte Ia antigens are indistinguishable by two-dimensional gel electrophoresis.
Authors: Osborne B A , Rudikoff S
Published: December 2022

Ia antigens have been found on the surface of B lymphocytes, macrophages, epidermal Langerhans cells and on certain transformed cells. Ia antigens have also been detected on the surface of thymocytes but the biosynthesis of these antigens by thymocytes has been difficult to demonstrate. We describe the labeling of murine thymocytes with 35S-methionine and the subsequent analysis of Ia antigens by two-dimensional polyacrylamide gel electrophoresis. Cell elimination experiments demonstrated that the Ia antigens detected were not of B cell origin and were synthesized by a Thy-1-positive thymocyte. Ia antigens from thymocytes were found to be indistinguishable from spleen Ia preparations. Since T cell I region determinants have been postulated to be involved in cellular recognition phenomena, models addressing this recognition must allow for the observation that T and B cell I region molecules detected by antisera such as A. TH anti-A. TL are indistinguishable by two-dimensional gel analysis and are thus unlikely to be involved in the generation of specificity in recognition.
Two distinct mechanisms of cytotoxicity by porcine alveolar macrophages in antibody-dependent and immobilized immune complex-dependent cellular cytotoxicity.
Authors: Rothlein R , Kim Y B
Published: December 2022

The mechanisms of cytotoxicity by porcine pulmonary alveolar macrophages (PAM) involved in antibody-dependent cellular cytotoxicity (ADCC) and immobilized immune complex-dependent cellular cytotoxicity (IIC-DCC) were investigated. The results indicate that IIC-DCC was inhibited by both catalase and thioglycollate broth whereas these peroxide scavengers had no effect on ADCC in an 18-hr chromium-release assay. Furthermore, it was found that when the PAM and red blood cell targets were cross-linked with PHA, catalase still completely eliminated IIC-DCC and had no effect on ADCC, which suggests that catalase is able to penetrate the lytic site when the effector and targets are cross-linked as in ADCC. The presence of cytochalasin B, which inhibits internalization of immune complexes by PAM and presumably prevents intracellular killing, also had no effect on the differential susceptibility of IIC-DCC and ADCC to catalase. Finally, it is shown that the nonspecific cytotoxicity generated by exposing PAM to immune complexes in suspension in conjunction with cytochalasin B, so that the immune complex-bound Fc receptor (FcR) cannot be internalized, also was susceptible to catalase. These data show that the lytic mechanism involved in the nonspecific cytotoxicity generated by exposing PAM to immobilized immune complexes or immune complexes in suspension in conjunction with cytochalasin B, both of which prevent the internalization of immune complex-bound FcR, is mediated solely by peroxide whereas the lytic mechanism involved in ADCC operates, at least partially, through a peroxide-independent mechanism.
Resistance of various strains of mycobacteria to killing by activated macrophages in vivo.
Authors: Orme I M , Collins F M
Published: December 2022

A variety of experimental infections with pathogenic mycobacteria are associated with the development of persistent disease, in which little or no changes in the numbers of the infectious organism can be detected. This report describes a simple experimental model designed to test the hypothesis that this persistence may reflect in part the ability of these organisms to resist the enhanced bacteriostatic and bactericidal properties acquired by host macrophages as a result of these mycobacterial infections. To examine this possibility mice were inoculated with test organisms at a time when these animals were expressing very high levels of nonspecific resistance, and hence macrophage activation, as a result of a prior intravenous infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG). The results show that the test organisms fall into three groups; (a) those, such as Mycobacterium tuberculosis, which were sensitive to the presence of activated macrophages, (b) those, such as Mycobacterium avium and Mycobacterium kansasii, which were insensitive, and (c) one organism, Mycobacterium intracellulare, in which progressive growth of the infection was significantly improved. These results are consistent with the hypothesis that some mycobacteria, particularly those associated with persistent disease, possess an intrinsic resistance to host bactericidal and bacteriostatic mechanisms in vivo.
Antibody-dependent leukocyte killing of Cryptococcus neoformans.
Authors: Miller G P , Kohl S
Published: December 2022

Cryptococcus neoformans is an encapsulated, yeast-like fungus which is pathogenic for man. The role of various facets of the immune response which prevent disseminated disease in most normal hosts is unclear. A chromium-release assay was developed using radiolabeled cryptococci to reexamine antibody-dependent cell-mediated killing of this fungus. For a small capsule strain this assay served as a qualitative measure of effector cell function and was correlated with an assay of lethal injury to the organism. Polymorphonuclear leukocytes rather than mononuclear cells were the most active effector cells, causing significant chromium release from the fungus at effector-to-target ratios as low as 3:1. Polymorphonuclear leukocytes and mononuclear cells from a patient with chronic granulomatous disease showed minimal antibody-dependent cell-mediated chromium release suggesting that the final fungicidal pathway may be similar in antibody-dependent and antibody-independent leukocyte killing of this organism.
The immunologic response of congenitally athymic rats to Schistosoma mansoni infection. I. In vivo studies of resistance.
Authors: Phillips S M , Bentley A G , Linette G , Doughty B L , Capron M
Published: December 2022

The responses of congenitally athymic (Nu/Nu) rats to an initial exposure and to re-exposure to Schistosoma mansoni were compared to those manifested by thymic reconstituted (Nu/Nu*TxR), heterozygous littermate controls (Nu/+) and the highly characterized Fischer rat strain. Congenitally athymic rats rejected the developing worms of an initial infection more slowly than did thymic reconstituted or heterozygous animals. These latter responses were highly comparable to those demonstrated by the Fischer rat. In addition, the congenitally athymic rats manifested lower peripheral blood eosinophilia in response to infection. Resistance to reinfection in athymic animals was impaired and associated with a decreased immunoinflammatory histologic response to hepatic intravascular parasites and to eggs lodged in the hepatic vasculature. There was little evidence of inflammatory responses involving degranulating eosinophils, lymphocytes, or macrophages in the athymic rats. Finally, athymic animals produced antibody that was less capable of passively transferring resistance in adoptive-challenge experiments; however, antibody produced in heterozygous animals conferred significant resistance when adoptively transferred to athymic animals. These results suggest that resistance to initial and subsequent challenge by S. mansoni infections in the rat is highly reliant upon T-dependent mechanisms that result in the production of antibody-dependent, possibly cell-mediated resistance. Additional studies utilizing in vitro analysis of a variety of antibody functions to define the mechanisms of T-dependent immunologic resistance in the congenitally athymic rat are the subject of the accompanying manuscript.
Macrophages as effector cells of protective immunity in murine schistosomiasis. VI. T cell-dependent, lymphokine-mediated, activation of macrophages in response to Schistosoma mansoni antigens.
Authors: James S L , Lazdins J K , Hieny S , Natovitz P
Published: December 2022

Macrophages from Schistosoma mansoni-infected mice kill significant numbers of skin stage schistosomula and murine fibrosarcoma cells in vitro. In order to determine whether the macrophage tumoricidal and larvicidal activation observed in mice as a result of S. mansoni infection are mediated through T cell-dependent (lymphokine) or B cell-dependent (antibody or immune complex) mechanisms, the development of macrophage populations with cytotoxic activity against schistosome larvae or tumor cells was monitored in S. mansoni-infected nude or mu-suppressed mice. Whereas peritoneal cells from S. mansoni-infected congenitally athymic mice had no activity in either assay, cells from mu-suppressed S. mansoni-infected mice showed cytotoxic activity equivalent to that of cells from untreated S. mansoni-infected counterparts. Cells from mu-suppressed uninfected mice were not activated. The mu-suppressed animals had no detectable nonspecific IgM or specific antischistosome IgM, IgG, or IgE antibodies and showed a 90% reduction in numbers of splenic IgM+ cells upon fluorescence activated cell sorter analysis. These results indicate that antibody is not required for in vivo activation of macrophages during S. mansoni infection. Further experiments showed that lymphoid cells from S. mansoni infected mice respond in culture with various specific antigens (such as living or dead whole schistosomula or soluble adult worm antigens) by production of factors capable of activating macrophages from uninfected control mice to kill schistosomula or tumor cells in vitro. Macrophage-activating factors were produced by T cell-enriched, but not T cell-depleted or B cell-enriched, populations from spleens of schistosome-infected mice in response to schistosome antigen. Similar lymphokines may be responsible for the macrophage activation observed during chronic murine schistosomiasis. These observations emphasize the potential contribution of T cell-mediated immune mechanisms in resistance to S. mansoni infection.
Recognition of Leishmania donovani antigens by murine T lymphocyte lines and clones. Species cross-reactivity, functional correlates of cell-mediated immunity, and antigen characterization.
Authors: Sheppard H W , Scott P A , Dwyer D M
Published: December 2022

Studies in man and experimental animals suggest that cell-mediated immunity is of primary importance in limiting the pathogenesis of cutaneous and visceral leishmaniasis. In an attempt to determine, more directly, the role of T lymphocytes and the nature of the antigens that activate them, we have propagated antigen-specific murine T lymphocyte lines and clones that proliferate in response to antigens present on the membrane of intact Leishmania donovani promastigotes. One such line cross-reacts with membrane antigens on seven other Leishmania species and, to a lesser extent, with antigens on African procyclic trypanosomes. T lymphocyte clones that also exhibited a broad range of species cross-reactivity were isolated. About 40% of these clones had highly restricted specificity, whereas 60% were more extensively cross-reactive. The parent line and some clones passively transferred footpad DTH when injected locally, and some secreted a lymphokine activity that elicited intracellular killing of amastigotes within infected macrophages. Although the proliferative response of most clones was H-2 restricted, two clones appeared to be reactive in the presence of allogeneic antigen presenting cells. The majority of the clones appeared to recognize carbohydrate containing antigens, and absorption with solid substrate-bound lectins indicated that these antigens contained both mannose and galactose ligands. The antigenic activity was also absorbed using either of two extensively cross-reactive anti-parasite monoclonal antibodies.
Evidence that anti-idiotype induced immunity to experimental African trypanosomiasis is genetically restricted and requires recognition of combining site-related idiotopes.
Authors: Sacks D L , Sher A
Published: December 2022

The ability of anti-idiotypic (anti-Id) antibodies to immunize mice against African trypanosomiasis independent of antigen has been confirmed. Of three allogeneic anti-Id antibodies raised against three protective monoclonal antibodies, each with specificity for the variant surface antigen of a clone of Trypanosoma rhodesiense, only one (anti-7H11 Id) was effective in immunizing BALB/c mice against homologous challenge. The immunity was associated with the more rapid and enhanced expression of the corresponding Id after infection. The immunity was restricted to mice bearing genes linked to Igh-Ca, which appeared to control expression of this Id both in response to infection and anti-Id treatment. Another Id, 11D5, appeared to be under similar genetic control. Anti-11D5 Id, however, was ineffective in immunizing mice against infection despite inducing high levels of Id bearing molecules before challenge. The immunizing potential of the respective anti-Id antibodies appeared to be related to the relative concentrations of antibodies reactive with idiotopes near to or within the antigen-combining site, which, in turn, determined the relative proportion of Id-bearing clones activated that had antigen binding activity.
IgE responses in human filariasis. II. Qualitative characterization of filaria-specific IgE.
Authors: Hussain R , Ottesen E A
Published: December 2022

Crossed radioimmunoelectrophoresis (CRIE) was used to characterize human IgE antibody responses to filarial parasites by using antigens derived from Brugia malayi (Bm) adult worms. A reference pool of patient sera was initially used to determine the sensitivity and specificity of CRIE. Because IgG-blocking antibodies interfered with IgE binding in certain sera, all sera were preabsorbed with protein A-Sepharose. As little as 50 ng of specific IgE antibody (determined by quantitative radioallergosorbent test [RAST]) in the reference pool bound to 20 of the 35 antigen precipitates in crossed immunoelectrophoresis. Increasing IgE antibody concentration did not increase the number of IgE-binding precipitates. Six patients from each of the three major clinical groups in lymphatic filariasis (i.e., tropical pulmonary eosinophilia [TE], chronic lymphatic pathology [CP], or circulating microfilaremia [MF]) were studied by CRIE with the use of a constant amount of IgE antibody (50 ng IgE anti-BmA). Distinct patterns of allergen recognition were observed among the groups. Individuals with TE recognized both anodic and cathodic antigens as allergens, whereas the other two groups recognized predominantly anodic antigens. The greatest number of allergens was recognized by patients with TE; this number ranged from nine to 18, whereas patients with CP or circulating MF recognized from six to 11 allergens. Although potentiated IgE responses at a quantitative level in parasitic helminth infections is a well-established phenomenon, our studies showing the diversity of antigens recognized as allergens indicate for the first time potentiated IgE responses at a qualitative level as well.
Influence of lymphokines on the anti-TNP-Ficoll response of normal and X-linked B lymphocyte-defective mice.
Authors: Xue B , Bell M K , Thorbecke G J
Published: December 2022

Immunodeficient CBA/N and F1 hybrids of CBA/N X SJL or DBA/2Ha mice were induced to make an antibody response to TNP-Ficoll by i.v. injections of lymphokines together with the antigen. The best responses (up to 12,000 PFC/spleen on day 4) were obtained by repeated i.v. lymphokine injections on days 0, 1, 2, and 3. Lymphokines obtained from PHA-stimulated LBRM-33 cells were less effective than those in supernatants (SN) from cocultures of SJL lymph node and gamma-RCS lymphoma cells, although in each case 100 U IL 2 were given per injection. Similar SN injections caused two- to threefold increases in responses of nondefective F1 hybrids. Pretreatment with lymphokine before TNP-Ficoll injection had no effect. Additional injection of monoclonal anti-IgD decreased the effect of lymphokine. Responses to TNP-Ficoll of CBA/J spleen cells were enhanced in vitro by SN as shown previously. Although responses by CBA/N spleen cells to TNP-polyacrylamide were increased by SN, however, responses to TNP-Ficoll could not be obtained with spleen cells from the xid mice in vitro.
Accessory cells in immune suppression. I. Role of I-A+ accessory cells in effector phase idiotype-specific suppression of myeloma function.
Authors: Moser G , Tominaga A , Greene M I , Abbas A K
Published: December 2022

The suppression of MOPC 315 myeloma cells by idiotype-specific effector Ts requires the presence of non-immune AC. This requirement was demonstrated in cultures where myeloma targets and Ts were separated by cell-impermeable membranes or were in direct contact. The AC were adherent, radioresistant, and present in peritoneal exudates and in FcR+ as well as FcR- fractions of low density splenocytes; they bore cell surface I-A determinants and did not have to be H-2 compatible with myeloma cells and Ts. These studies demonstrate a novel role for Ia+ AC in immune regulation, and suggest that their accessory function may involve processing of T lymphocyte-derived suppressor factors or presentation of such factors to target cells.
Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens.
Authors: Lanier L L , Le A M , Phillips J H , Warner N L , Babcock G F
Published: December 2022

The functional and phenotypic characteristics of cells in human peripheral blood that mediate "natural killer" (NK) cytolysis have been examined with the use of multiparameter flow cytometry analysis and cell sorting. Essentially, all lymphocytes expressing NK and ADCC activity reacted with the anti-Leu-11a monoclonal antibody. The Leu-11a antigen was expressed on cytotoxic large granular lymphocytes (LGL), neutrophils, and basophils, but was not present on B cells, mitogen-activated T lymphoblasts, or Leu-1+ and Leu 4+ resting T cells. Anti-Leu-11a antibody selectively inhibited the binding of FITC heat-aggregated IgG complexes to granulocytes and LGL, and it may recognize a type of Fc receptor on these cells. Two-color FACS cell sorting indicated the existence of four lymphocyte subsets defined by the expression of Leu-11a and Leu-7 antigens. The Leu-11a+, -7- cells were highly active in 4-hr NK assays with the use of 51Cr-labeled K562 as the target. In contrast, the Leu-11a-, -7+ cells demonstrated weak activity and the Leu-11a-, -7- cells demonstrated no activity. The function of the Leu 11a+, -7+ cells varied considerably among several individuals examined. Multiparameter analysis with the use of two-color flow cytometry was used to determine the relationship between the expression of these NK-associated antigens and T and B cell-associated markers. These data indicate that considerable heterogeneity exists within human peripheral lymphocytes with regard to cell phenotype and function, but that several defined cellular subsets can be clearly revealed by using multiparameter FACS analysis and sorting.