bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of the Fc receptor of human lymphoid cells by antisera-recognizing determinants of the hla system.
Authors: Solheim B G , Thorsby E , Möller E
Published: June 2004

The inhibitory effect of HLA antisera on Fc receptors of human lymphoid cells was investigated. The ability of lymphoid cells to form rosettes (FcRFC) with antibody-coated sheep red blood cells and to function as effector cells (K cells) in antibody-dependent cell-mediated cytotoxicity were used as assay systems. We found that antisera recognizing determinants of the HLA-A, -B, and -C series had no effect on FcRFC, while a specific inhibitory effect was observed of antisera probably reacting with determinants identical to or closely associated with those of the HLA-D series. This inhibitory effect was retained in the F(ab')2 fragments. Specific inhibition of K cells was observed with all HLA antisera, but this effect was lost in the F(ab')2 fragments. We conclude that the Fc receptor of rosette-forming lymphocytes may be closely associated with products of the HLA-D region. This is analogous to the association between the Fc receptor and the Ia antigens on murine rosette-forming B lymphocytes.
Synthesis of basement membrane collagen by cultured human endothelial cells.
Authors: Jaffe E A , Minick C R , Adelman B , Becker C G , Nachman R
Published: June 2004

Studies were performed to determine if cultured human endothelial cells synthesized basement membrane collagen. In culture, endothelial cells were attached to grossly visible membranous structures which on light microscopy were composed of ribbons of dense, amorphous material. On transmission electron microscopy, these membranous structures consisted of amorphous basement membrane, and material morphologically similar to microfibrils and elastic fibers. By immunofluorescence microscopy, these membranous structures stained brightly with antisera to human glomerular basement membrane. Cultured endothelial cells incorporated [3H]proline into protein; 18% of the incorporated [3H]proline was solubilized by purified collagenase. When endothelial cells were cultured with [14C]proline, 7.1% of the incorporated counts were present as [14C]hydroxyproline. Cultured endothelial cells were labeled with [3H]glycine and [3H]proline and digested with pepsin. The resulting fractions on analysis by SDS-polyacrylamide gel electrophoresis contained two radioactive protein peaks of mol wt 94,200 and 120,500. Both these peaks disappeared after digestion with purified collagenase. The peak of mol wt 120,500 corresponds to that of alpha1 (IV) collagen; the peak of the mol wt 94,200 probably corresponds to that of alpha1 (III) collagen. Thus, cultured human endothelial cells synthesize material which is morphologically and immunologically like amorphous basement membrane and biochemically like basement membrane collagen. Cultured endothelial cells probably also synthesize material which is morphologically similar to microfibrils and elastic fibers.
Differential susceptibility of neonatal and adult murine spleen cells to in vitro induction of B-cell tolerance.
Authors: Cambier J C , Kettman J R , Vitetta E S , Uhr J W
Published: June 2004

The relative susceptibility of neonatal and adult murine splenocytes to induction of B-cell tolerance was studied in vitro. Adult cells required approximately 1,000-fold more trinitrophenyl-human gamma globulin to be rendered tolerant than did cells from 9- to 12-day-old neonates. The potential effects of suppressor T cells were excluded by pretreating the cultured B cells with anti-Thy-1 and C' and the helper T cells with anti-Ly-2.2 and C'. The possible role of cell surface immunoglobulin isotypes in contributing to this observed difference is discussed.
Protection against group B meningococcal disease. I. Comparison of group-specific and type-specific protection in the chick embryo model.
Authors: Frasch C E , Parkes L , McNelis R M , Gotschlich E C
Published: June 2004

Protection against group B meningococcal infection was examined using the chick embryo. 12-day-old embryos were challenged intravenously with various meningococcal strains. The chick embryo has an active reticuloendothelial system but lacks functional complement. In this model we found that protection against group B infection was primarily group specific. The group B polysaccharide antibody is an effective opsonin, but is a very poor bactericidal antibody. In contrast, the serotype antibody was bactericidal but only slightly protective in the chick embryo where protection is primarily phagocytic in nature. The group-specific and type-specific antibodies are strongly synergistic. Minute amounts of group B polysaccharide antibody caused a very significant increase in the protective effects of the serotype antibody.
T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells.
Authors: Herzenberg L A , Okumura K , Cantor H , Sato V L , Shen F W , Boyse E A , Herzenberg L A
Published: June 2004

Allotype suppressor T cells (Ts) generated in SJL X BALB/c mice specifically suppress production of antibodies marked with the Ig-1a allotype. The studies presented here show that allotypes Ts suppress by specifically removing helper T cell (Th) activity required to facilitate differentiation and expansion of B cells to Ig-1b antibody-forming cells. We show first that Ts and Th belong to different T-cell subclasses as defined by Ly surface antigens. Ts are Ly2+Lyl- and thus belong to the same subclass as cytotoxic precursor and effector cells; Th are Lyl+Ly2- cells and thus belong to the subclass containing cells which can exert helper functions and initiate delayed hypersensitivity reactions. Placing these cells in these two subclasses shows that Th are different from Ts and suggests that they play different roles in regulating antibody responses. The difference in these roles is defined by the evidence presented here showing that Ts attack Th and regulate the antibody response by specifically regulating the availability of Th activity. We show that in allotype suppressed mice, Ts which suppress Ig-1b antibody production have completely removed the Th activity of helping Ig-1b cells without impairing Th activity which helps other IgB B cells. These findings imply the existence of allotype-specific Th for Ig-1b cells (Ig-1b Th). We directly establish that Ig-1b cells require such help by showing that carrier-primed spleen cells from Iga/Iga congenic hybrids help Ig-1a B cells from hapten-primed Igb/Iga donors but do not help Ig-1b B cells from the same donor in the same adoptive recipient.
Murine B-cell subpopulations responsive to T-dependent and T-independent antigens.
Authors: Lewis G K , Ranken R , Nitecki D E , Goodman J W
Published: June 2004

Strain A/J mice made secondary indirect plaque-forming cell (PFC) responses to azobenzenearsonate (ABA) conjugates of giant keyhole limpet hemocyanin (KLH), a thymic-dependent antigen, but not to conjugates of Ficoll, a T-independent antigen. ABA-Ficoll was also unable to elicit a response in animals primed with ABA-KLH, which have an expanded anti-ABA memory cell pool. On the other hand, ABA-Ficoll rendered mice unresponsive to ABA-KLH when administered before priming or boosting with the T-dependent immunogen. Hence, the T-independent antigen was able to tolerize but unable to trigger B-memory cells responsive to the T-dependent antigen. A/J mice immunized with dinitrophenyl conjugates of Ficoll or bovine IgG (BGG) made vigorous IgM and IgG PFC responses. PFC responses to ABA-KLH and 2,4-dinitrophenyl (DNP)-BGG were abrogated by depleting mice of C3 with cobra venom factor, whereas the IgM and IgG PFC responses to DNP-Ficoll were unaffected. B lymphocytes were fractionated on the basis of receptors for C3 and the subpopulations were assayed for in vitro PFC responses to DNP-Ficoll. Very little response was obtained from complement receptor lymphocyte [CRL(+)] B cells, whereas CRL(-) cells were more responsive than unfractionated B cells. Both populations responded to a polyclonal B-cell mitogen (lipopolysaccharide). On the other hand, the in vitro PFC response to a T-dependent antigen (sheep erythrocytes) correlated with the presence of CRL(+) B cells in the cultures. However, a minor component of this response, sensitive to anti-Thy-1 serum, was made by CRL(-) B cells, indicating the existence of subpopulations of T-dependent B cells with different signalling requirements. The results suggest that most B cells responsive to T-dependent antigens possess receptors for C3 and that C3 plays an obligatory role in the response of these cells. A distinct subpopulation of B cells which lack C3 receptors respond to T-independent antigens. The precursors of PFC for the ABA epitope reside largely or exclusively in the CRL(+) compartment in A/J mice, whereas precursors for the DNP determinant are found in both compartments.
Heterogeneity of murine regulatory T cells. I. Subpopulations of amplifier and suppressor T cells.
Authors: Whisler R L , Stobo J D
Published: June 2004

Immunization of C3H/HeJ mice with 4 X 10(9) SRBC yields a whole splenic T-cell population which can, upon transfer, specifically suppress recipient direct and indirect plaque-forming cells (PFC) responses to sheep erythrocytes (SRBC). Discontinuous bovine serum albumin density gradient fractionation of these T cells demonstrated a population of low density T cells which augmented and a population of high density T cells which suppressed recipient responses irrespective of the number of T cells transferred. Moreover, infusion of admixtures of low and high density cells resulted in intermediate regulatory functions which could be predicted by knowing the regulatory capacity of each population alone. In addition to heterogeneity existing among regulatory T cells as regards amplification and suppression, it appeared that heterogeneity existed within the suppressor T population. Thus, T cells capable of inhibiting direct PFC could be distinguished from those suppressing indirect PFC by their differential localization in peripheral lymphoid tissue, differences in the dissipation of suppressive influences during incubation at 37 degrees C, and by differences in the possible requirement for adherent cell populations. While the relative frequency of both low density amplifier and high density suppressor cells increased with the dose of SRBC used for their induction, it appeared that suppressor cells might be generated in response to feedback signals from amplifier cells. These studies indicate that further delineation of heterogeneity existing within suppressor populations may be helpful in defining mechanisms required for the induction and manifestation of suppressive regulatory forces.
Helper function of T cells depleted of alloantigen-reactive lymphocytes by filtration through irradiated F1 hybrid recipients. I. Failure to collaborate with allogeneic B cells in a secondary response to sheep erythrocytes measured in vivo.
Authors: Sprent J , von Boehmer H
Published: June 2004

Helper T cells were obtained by injecting heavily irradiated semiallogeneic mice with lymph node cells from H-2-incompatible parental strain mice primed with sheep erythrocytes (SRC) 2 mo before. Thoracic duct lymphocytes collected from the recipents 18-40 h later (nearly all of which were theta-positive and of donor origin) were totally and specifically unresponsive against host-type determinants in mixed-lymphocyte culture. The filtered cells were transferred to irradiated semiallogeneic mice together with SRC and anti-theta-serum-treated (B) cells from SRC-primed syngeneic, semiallogeneic, or allogeneic mice. When antibody-forming cells were measured in the spleen 5-9 days later, effective IgM and IgG collaborative responses were observed with both syngeneic and semiallogeneic B cells but not with allogeneic B cells. No evidence was found that the failure to obtain collaboration with the allogeneic B cells was due to inhibition of the B cells by the T cells or vice versa.
Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies.
Authors: Lindstrom J M , Engel A G , Seybold M E , Lennon V A , Lambert E H
Published: June 2004

Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG.
Studies on the mechanism of phagocytosis. II. The interaction of macrophages with anti-immunoglobulin IgG-coated bone marrow-derived lymphocytes.
Authors: Griffin F M , Griffin J A , Silverstein S C
Published: June 2004

We have examined the effect of the distribution of anti-immunoglobulin IgG molecules on the surface of bone marrow-derived lymphocytes upon the interaction of these cells with macrophages. Lymphocytes which were diffusely coated with antibodies to surface immunoglogulin were ingested by macrophages. Lymphocytes which had the same number of anti-immunoglobulin IgG molecules redistributed to one pole of the surface bound to the macrophages' Fc receptors but were not ingested. These results confirm our previous hypothesis that ingestion of an immunologically coated particle requires the sequential, circumferential binding of specific receptors on the plasma membrane of a phagocytic cell to immunologic ligands distributed over the entire particle surface. Macrophages which had bound capped lymphocytes by the macrophages' Fc receptors removed the immune complex caps from the lymphocyte surface without destroying the lymphocytes. These lymphocytes remained attached to the macrophage surface. The finding that macrophages can phagocytize immune complexes from the surface of a cell without destroying the cell to which these complexes are attached may be important in understanding the effects of antigens and antibodies on cells participating in a humoral immune response, in identifying the mechanisms by which chronic viral infections are established, and in defining the roles of blocking antibodies in tumor immunity.
Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules.
Authors: Stamper H B , Woodruff J J
Published: June 2004

An in vitro model is described for studying the interaction between lymphocytes and high-endothelial venules (HEV) of lymph nodes. Rat or mouse lymphocytes which were layered over fixed sections of syngeneic lymph nodes adhered selectively to the endothelium of HEV but did not bind to other vascular endothelia. Evidence is presented that adherence to HEV in vitro is a property of recirculating lymphocytes and not a characteristic of cells which are unable to home into lymph nodes in vivo.
Murine t factors: an association between alleles at t and at H-2.
Authors: Levinson J R , McDevitt H O
Published: June 2004

Lymphocytes from tx-mutant mice have a definite and consistent pattern of reactivity in MLR. Cells from t-mutant mice within a complementation group usually fail to stimulate each other, while cells from mutants in different complementation groups stimulate each other strongly. This indicates that tx-mutant types are associated with certain H-2 haplotypes, and that members of any give complementation group share the same H-2 haplotype.
Alternative pathway of complement: demonstration and characterization of initiating factor and its properdin-independent function.
Authors: Schreiber R D , Götze O , Müller-Eberhard H J
Published: June 2004

A novel component of the properdin system has been discribed which represents a heretofore unrecognized human serum protein. The protein has been tentatively termed the initiating factor (IF) because it functions in the initial reaction of the properdin pathway. IF is a 170,000 dalton beta-pseudoglobulin which is composed of two presumably identical 85,000 dalton chains linked by disulfide bonds. The protein reacts with antibody to nephritic factor, which is defined by its activity and is found in the serum of patients with certain nephritides. The activity of IF is heat stable. Upon treatment of serum with activators of the alternative pathway, the initial C3 convertase is assembled from IF, Factors D and C, C3, and magnesium without participation of properdin. It is the function of the enzyme to deposit C3b on the surface of the activator particles, thereby affording generation of the solid phase enzymes of the pathway, a process that is a prerequisite for properdin activation. By exposure to low pH, IF assumed the electrophoretic mobility of psi-globulin and acquired the ability to generate without activators a fluid phase C3 convertase in serum. Serum depleted of IF did not allow activation of the properdin pathway. Serum depleted of properdin did permit activation of the pathway and expression of cytolytic activity. These results raise the possibility that IF represents the recognition unit of the pathway.
Murine model for human secondary amyloidosis: genetic variability of the acute-phase serum protein SAA response to endotoxins and casein.
Authors: McAdam K P , Sipe J D
Published: June 2004

The serum precursor SAA of the secondary amyloid protein AA has been detected by solid-phase radioimmunoassay as a normal serum alpha-globulin of mol wt 160,000, which dissociates to a more stable 12,500 dalton moiety on treatment with formic acid. In 12 strains of mice, including T-cell-deficient nude mice, treated with the amyloid-inducing agents lipopolysaccharide (LPS) or casein, SAA behaved as an acute-phase reactant. SAA concentration rose to about 750 mug/ml by 24 h and returned to less than 1 mug/ml by 48 h. Since the amyloid-resistant colchicine-treated mice and AJ mice had a normal SAA response to LPS, it appears that their resistance to amyloid induction is due to the nature of their SAA processing rather than decreased SAA production. C3H/HeJ mice, which have defective B-lymphocyte responses to LPS, required extremely high dosages of LPS to cause SAA elevation, although their SAA response to casein was normal. This suggests that SAA is an acute-phase protein produced as a result of B-lymphocyte stimulation. Preliminary evidence suggests that at the height of an acute SAA response, liver homogenates are particularly rich in protein AA cross-reacting material.
Cell surface antigens of human malignant melanoma. II. Serological typing with immune adherence assays and definition of two new surface antigens.
Authors: Shiku H , Takahashi T , Oettgen H F
Published: June 2004

Immune adherence assays revealed that 10 out of 18 melanoma patients had demonstrable antibody to surface antigens of autologous cultured melanoma cells, with serum titers ranging from 1/4 to 1/160. Autologous fibroblasts showed no reactions with these sera. Antibody from individual patients showed reproducible temperature preference for maximal reactivity. Two new melanoma antigenic systems were defined in this study. The first, BD, was restricted to autologous melanoma and could not be demonstrated in absorption tests on 12 allogeneic melanoma cell lines. The other, AH, was found on 5 of 12 melanomas and represents a class of shared melanoma surface antigens. Neither BD nor AH antigen was found on normal cells from autologous, allogeneic, or xenogeneic sources or on any nonmelanoma tumor cell line. Methods are now available to develop a comprehensive serological classification of the surface antigens of melanoma.
Decline in the growth potential of spleen-colonizing bone marrow stem cells of long-lived aging mice.
Authors: Albright J W , Makinodan T
Published: June 2004

The growth capacity of femoral bone marrow stem cells from young and old long-lived mice was assessed in the spleen of X-irradiated young and old syngeneic recpients by determining: (a) the number of stem cells colonizing the spleen, (b) the rate of incorporation of 125I-labeled iododeoxyuridine by proliferating colony cells, and (c) the number of cells present in the largest colonies at the end of the growth phase.We found that the growth capacity of stem cells declined with age. We further found that the spleen-seeking and spleen colony growth capacities of old stem cells remained characteristically old even after they were allowed to self-replicate in the bone marrow of young recipients for an extended period of time. On the other hand, the spleen colony growth capacity of young stem cells could be reduced by allowing them to self-replicate in old recipients. These results suggest that the growth capacity of old stem cells is an intrinsic characteristic which cannot be readily altered, but that of young stem cells can be aged in an accelerated manner by allowing them to self-replicate in old recipients. An additional reduction was noted in the frequency of both young and old stem cells colonizing the spleen of old recipients and in the cell density of the largest colonies produced. These results indicate that factors extrinsic to the stem cells are also responsible for the decline with age in their spleen colony growth capacity.Thus, the growth capacity of old stem cells in old recipients could be as low as 10% that of young stem cells in young recipients.
Antibodies in human sera to oncorna virus-like proteins from normal or leukemia marrow cell cultures.
Authors: Louie S , Curtis J E , Till J E , McCulloch E A
Published: June 2004

Some human marrows in culture release particles with oncornavirus-like properties. This study was designed to examine the immunological properties of similar particles in human marrow culture supernates. Leukemic and nonleukemic marrows were cultured for 5-7 days in the presence of [14C]uridine and [3H]leucine or [3H]glucosamine. Labeled supernatant components banding in sucrose gradient densities of 1.20-1.24 g/ml were used as antigen in a double antibody immunoprecipitation assay. The assay was validated by end point titrations and competition with unlabeled antigen; purified myeloma proteins were used as negative controls. Cross-reactivity with mammalian oncornaviruses, as judged by competitive inhibition of precipitation by these viruses, was slight and at the border of the sensitivity of the method. Precipitated antigens analyzed by SDS polyacrylamide gel electrophoresis contained three distinct polypeptides of about 70,000, 45,000 and 30,000 mol wt; these comigrated with the gp 70, pg 45, and p 30 of a murine leukemia virus. Similar polypeptides were obtained from both leukemic and nonleukemic marrow culture supernates. As determined by the radioimmunoprecipitation assay, 32 of 45 leukemic sera (71%), 36 of 45 normal sera (80%), 15 of 19 sera from family contacts of leukemic patients (79%), 14 of 21 cord blood specimens (67%), and 21 of 23 sera (91%) from patients with systemic lupus erythematosus had detectable antibody activity.
Nature of the antigenic complex recognized by T lymphocytes. I. Analysis with an in vitro primary response to soluble protein antigens.
Authors: Thomas D W , Shevach E M
Published: June 2004

In order to analyze the genetic factors involved in the regulation of macrophage-T-cells interaction we have developed an in vitro primary response to soluble protein antigens in which nonimmune guinea pig T cells can be sensitized and subsequently challenged in tissue culture with antigen-pulsed macrophages. Antigen-specific T-cell activation, as measured by increased DNA synthesis, occurred when syngeneic antigen-pulsed macrophages were used for both initial sensitization and secondary challenge. No T-cell activation occurred when allogeneic antigen-pulsed macrophages were used for secondary challenge of cells primed when syngeneic macrophages. When allogeneic antigen-pulsed macrophages were used in both primary and secondary cultures it was difficult to assess antigen-specific stimulation due to the substantial mixed leukocyte reaction. However, when T cells from F1 animals were primed with parental antigen-pulsed macrophages they responded only to the parental macrophages used for initial sensitization but not to those of the other parent. These results are discussed with respect to T-cell recognition of a complex antigenic determinant which may include I-region gene products.
Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses.
Authors: Gresser I , Tovey M G , Maury C , Bandu M T
Published: June 2004

The effect of potent sheep anti-mouse interferon globulin was investigated in several different experimental virus diseases of mice. In anti-interferon globulin-treated mice infected intraperitoneally with herpes simplex virus (HSV) type I, the latent period was shortened, and the overall LD50 was increased several hundredfold compared to virus-infected control mice. When HSV was inoculated subcutaneously all anti-interferon globulin-treated mice died, whereas only 5% of virus-infected control mice died. Subsequent treatment with anti-interferon globulin of previously HSV-infected mice did not result in reactivation of HSV. Treatment of adult mice with anti-interferon globulin resulted in an earlier appearance of MSV-induced tumors, a greater number of mice bearing tumors, an increase in tumor size, and an increase in the duration of tumors. All tumors eventually regressed despite reinjection of anti-interferon globulin. Anti-interferon globulin treatment resulted in a rapid onset of disease and death in adult mice inoculated (intranasal) with VSV and in newborn mice infected with NDV. Anti-interferon globulin exerted no effect on the course of influenza virus infection of mice. We conclude that the early production of interferon is an importane element in the response of the mouse to several viruses exhibiting different pathogeneses.
Connective tissue origin of the amyloid-related protein SAA.
Authors: Linder E , Anders R F , Natvig J B
Published: June 2004

Protein SAA is a serum protein related to the major constituent of secondary amyloid fibrils, protein AA, and has been suggested to be a precursor of the amyloid protein AA. In the present study, the origin of SAA was investigated by studying human fetal tissues and cultured human fetal fibroblasts with the indirect immunofluorescence technique. Anti-SAA antibodies reacted strongly with cultured fibroblasts producing a fine fibrillary cytoplasmic staining and with extracellular fibrils in loose connective tissues and vessel walls. The reactions were specifically inhibited by absorption with degraded amyloid material, isolated protein AA, isolated protein SAA, and sera from patients with elevated levels of SAA. In contrast, no inhibition was seen with amyloid fibril material devoid of AA protein or by human sera in which SAA was not detectable by double-diffusion tests. These observations showed that SAA-like material is produced by fibroblasts and indicate that it is a normal constituent of developing extracellular connective tissue fibers.
The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen.
Authors: Naruse T , Fukasawa T , Hirokawa N , Oike S , Miyakawa Y
Published: June 2004

The renal tubular epithelial antigen (Tub-Ag) of rats was solublized by Pronase and purified by gel filtration and acrylamide gel electrophoresis. Purified Tub-Ag was a glycoprotein with S20,W value of 8.4. Utilizing radiolabeled Tug-Ag, a sensitive radioimmunoassay for Tub-Ag and homologous antibody (anti-Tub-Ag) was developed. Tub-Ag activity associated with a protein of the same molecular size was demonstrated in the serum, as well as in Pronase extracts of all the organs tested, including kidney, liver, lung, spleen, intestine, stomach, and heart. The physiochemical properties of the Tub-Ag of rats and its distribution were essentially the same as the Tub-Ag of humans, which had been found in immune deposits in the kidney of some patients with idiopathic membranous glomerulonephritis. Rats were immunized with the purified Tub-Ag emulsified in Freund's complete adjuvant and followed for Tub-Ag and anti-Tub-Ag in the serum, as well as for proteinuria and immunohistological changes in the kidney. Serum Tub-Ag dropped sharply after 20 days, when anti-Tub-Ag appeared in the circulation. Persistent, massive proteinuria appeared still later, more than 30 days after injection, when anti-Tub-Ag disappeared and Tub-Ag reappeared in the serum of some of those rats. In others, anti-Tub-Ag in the serum persisted throughout the observation period of 90 days. The pathology of the kidney of the rats with proteinuria was that of a typical membranous glomerulonephritis; thickening of glomerular capillary walls with granular deposits of gamma-globulin and Tub-Ag was observed. On the basis of these results, Tub-Ag in the serum, probably released from cellular membranes of various organs as a physiological metabolite, is considered to maintain the pathological process in the kidney by providing the antigen continuously to form immune complexes.
Correlation of suppressor cell development in parental and F1 hybrid mouse strains with the growth of a parental tumor in vivo.
Authors: Levy R B , Waksal S D , Shearer G M
Published: June 2004

Parental AKR/J, and AKB6F1 and AKD2F1 hybrid mice were injected subcutaneously with a spontaneously arising AKR/J tumor. The highly responsive AKB6F1 strain never exhibited any depression of immune functioning during the course of tumor growth and regression. The (AKR/J) intermediately responsive strain, while able to generate a successful anti-tumor response, did display a transient reduction of immunological capability, but only during the period tumor growth and not during tumor regression. Cells able to suppress antibody, but not cell-mediated responses, were found. The unresponsive AKD2F1 strain was characterized by both a marked depression of immune responsiveness, as well as the generation of suppressor cells to both antibody, and later, cell-mediated responses. Depression of immune responsiveness, and the generation of suppressor cells, appeared to correlate with the strength or weakness of the anti-tumor response in these strains of mice.
Specific transplantation tolerance induced by autoimmunization against the individual's own, naturally occurring idiotypic, antigen-binding receptors.
Authors: Binz H , Wigzell H
Published: June 2004

Serum or urine from normal adult Lewis rats can be shown to contain detectable amounts of idiotypic, antigen-binding receptors with specificity for the major histocompatibility complex locus antigens of the rat, the Ag-B locus antigens. Such purified naturally occurring receptor molecules, be they of T- or B-lymphocyte origin, can be used in a polymerized form to provoke the production of auto-anti-idiotypic antibodies when injected back into normal Lewis rats. As a consequence of this autoimmunity, lymphocytes of these Lewis rats can be shown to be depleted of cells carrying the relevant idiotypic receptors signifying reactivity against a given Ag-B locus-determined antigen(s). This specific lack of idiotypic lymphocytes is manifested as a selective loss of reactivity against the relevant Ag-B-incompatible antigens as measured by graft versus host or MLC reactions. Furthermore, autoimmune Lewis rats display specific transplantation tolerance against the skin grafts from the relevant strain, as demonstrated by specific prolongation of graft survival. A further indication of the specific tolerence state of these rats comes from the highly reduced ability to produce circulating antibodies against the relevant Ag-B antigens. No side effects of these autoimmunization procedures have been noted so far. It would thus seem clear that a prolonged state of specific transplantation tolerance can be achieved via autoimmunization against the individual's naturally occurring idiotypic, antigen-binding receptors.
2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages. I. Description of the inhibitory effect.
Authors: Michl J , Ohlbaum D J , Silverstein S C
Published: June 2004

Incubation of normal or thioglycollate-elicited mouse peritoneal macrophages with 2-deoxy-D-glucose (2-dG) inhibits the capacity of these macrophages to phagocytize IgG- or complement-coated particles via their Fc and C3 receptors. 2-dG has no inhibitory effect on the capacity of these macrophages to phagocytize latex or zymosan particles, which are ingested in the absence of specific opsonins, and it does not inhibit binding of IgG- or C3-coated particles to their respective receptors on the macrophage's plasma membrane. 2-dG exerts its inhibitory effect on the macrophage and not on the opsonized particle. The inhibition is independent of particle size, occurs within 15-30 min of addition of this glucose analogue to the medium at 37 degrees C, cannot be overcome by supra-agglutinating amounts of opsonizing antibody, and is completely reversible by substitution of 5.5 mM glucose for 50 mM 2-dG in the medium. Addition of equimolar amounts of glucose or mannose, but not of fructose, galactose, fucose, or glucosamine, to medium containing 50 mM 2-dG results in substantial reversal of the inhibitory effect of 2-dG on Fc and C3 receptor mediated phagocytosis.
2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages II. Dissociation of the inhibitory effects of 2-deoxyglucose on phagocytosis and ATP generation.
Authors: Michl J , Ohlbaum D J , Silverstein S C
Published: June 2004

Macrophages incubated in 2-deoxy-D-glucose (2-dG)-containing medium showed a marked decrease in cellular ATP content, and were unable to ingest IgG- and complement-coated erythrocytes via the corresponding membrane receptors for these ligands. However, the inhibitory effects of 2-dG on Fc- and C3 receptor-mediated phagocytosis were not a consequence of lowered macrophage ATP levels since addition of glucose or mannose to the culture medium restored the capacity of the macrophages to ingest IgG- and C3-coated particles without increasing ATP levels. These results indicate that Fc- and C3 receptor-mediated phagocytosis (opsonin dependent) differs qualitatively from the ingestion of latex and zymosan particles (opsonin independent); they suggest that the same regulatory molecules govern the responses of phagocytic cells to signals initiated by both the Fc and C3 receptors. The possibility that these molecules are regulated by glycosylation is discussed.
5'-Nucleotidase activity of mouse peritoneal macrophages. II. Cellular distribution and effects of endocytosis.
Authors: Edelson P J , Cohn Z A
Published: June 2004

The diazonium salt of sulfanilic acid (DASA) can inactivate about 80% of the total 5'-nucleotidase of viable macrophages. The remaining 20% can be inactivated if the cells are first lysed in detergent, and presumably represents an intracellular pool of 5'-nucleotidase. The bulk of this pool may represent cytoplasmic vesicles derived from plasma membrane by endocytosis. This internal compartment is expanded up to threefold immediately after the cells have ingested a large latex load. This is consistent with previous observations on the internalization of 5'-nucleotidase in latex phagosomes. In latex-filled cells this intracellular pool of enzyme is inactivated over a few hours, and the cells then slowly increase their enzyme activity to nearly normal levels. However, 24 h after latex ingestion the metabolism of 5'-nucleotidase in these recovered cells is abnormal, as the rate of enzyme degradation is about twice the normal rate, and the DASA-insensitive enzyme pool in these cells is strikingly diminished. This may reflect effects of the accumulated indigestible particles on the fate of incoming pinocytic vesicles or on newly synthesized plasma membrane precursor. Another endocytic stimulus, concanavalin A, also reduces the total cell 5'-nucleotidase activity. This effect, which is time and temperature dependent, can be prevented by the competitive sugar alpha-methyl mannose. The concanavalin A inhibition can be reversed in the absence of new protein synthesis or in cells cultivated in serum-free conditions. It is not known whether the effect of concanavalin A on 5'-nucleotidase depends upon the interiorizaiton of plasma membrane or is strictly associated with events at the cell surface.
Some properties of antisera to serum amyloid A protein (SAA): inhibition of precipitation by complexing of SAA to albumin.
Authors: Franklin E C
Published: June 2004

Three potent rabbit antisera to human serum amyloid A protein (SAA) appear to be directed exclusibely to the carboxy terminal region not shared with the tissue amyloid A protein. Since binding to albumin completely blocks the reaction of these antisera with the antigen, and since SAA exists in serum complexed to albumin, the anti-SAA cannot be used to detect or quantitate this serum component. The possibility that similar problems will be encountered with immunoassays for molecules that exist complexed to other proteins is discussed.
Spontaneous redistribution of surface immunoglobulin in the motile B lymphocyte.
Authors: Schreiner G F , Braun J , Unanue E R
Published: June 2004

This paper reports that B cells undergoing translatory motion spontaneously segregate their surface Ig to one portion of their plasma membrane. The spontaneous redistribution of surface Ig was found to be: (a) selective, concanavalin A-dependent on translatory motion and energy metabolism. Abundant B cells undergoing motility were found after cultures in lipopolysaccharide or trypsin, or after brief exposure to cholinergic drugs.
Concanavalin A-mediated binding and sphering of human red blood cells by homologous monocytes.
Authors: Guerry D , Kenna M A , Schrieber A D , Cooper R A
Published: June 2004

Human red blood cells sensitized with concanavalin A became bound to homologous peripheral blood monocytes. Binding occured at a concentration of 10(5) molecules of tetrameric Con A per red blood cell (RBC) and increased with additional Con A. RBC binding began within 5 min and was maximal at 90 min. Phagocytosis of sensitized RBCs was minimal. RBC attachment was prevented by 0.01 M alpha-methyl-D-mannopyranoside, and, once the RBC-monocyte rosette was established, bound RBCs were largely removed with this specific saccharide inhibitor of Con A. RBCs attached to monocytes became spherocytic and osmotically fragile. The recognition of concanavalin A (Con A)-coated RBCs was not mediated through the monocyte IgG-Fc receptor. These studies demonstrate that, like IgG and C3b, Con A is capable of mediating the binding of human RBCs to human monocytes. Red cells so bound are damaged at the monocyte surface.
Multiple H-2-linked immune response gene control of H-2D- associated T-cell-mediated lympholysis to trinitrophenyl-modified autologous cells: Ir-like genes mapping to the left of I-A and within the I region
Authors: Schmitt-Verhulst A , Shearer GM
Published: June 2004

One of the more recent associations of the murine H-2 major histocompatibility complex (MHC) with immune function has been the finding that cytotoxic T-effector cells generated by sensitization with viral-infected (1-6), chemically modified (7-9), or weak transplantation antigen-associated (10,11) syngeneic cells can efficiently lyse target cells which express the same viral, chemical, or weak antigenic agent, and which share the H-2K and/or H-2D regions of the MHC with the responding and/or stimulating cells. Furthermore, an additional contribution of a gene(s) within the H-2 complex has been demonstrated which controls immune response potential (Ir genes) in the generation of cytotoxic effector cells to trinitrophenyl (TNP)-modified self components (12,13). In such studies it was found that certain B10 congenic strains generated good cytotoxic responses to both TNP- modified H-2K and H-2D region products, whereas other B10 congenic strains exhibited preferential or exclusive reactivity against TNP-modified H-2K region products. Some of these recombinant strains differing in response potential to TNP- modified H-2D products expressed the same haplotype at the D end, but differed at the K end of H-2. The low responsiveness observed in the B10.A strain to TNP-modified H-2D(d) when compared to B10.D2 and (B10.A x B10.D2)F(1) for the same specificity, suggested a role of dominant Ir genes which map in K, I-A, I-B, I-J, and/or I-E (12, 14).

In the present report an attemnpt was made to further map within the MHC the Ir gene(s) controlling cell-mediated lympholysis (CML) to TNP-modified H-2D(d), by using recombinant mouse strains on the A and B10 backgrounds. Irrespective of the genetic background, the s and k haplotypes at the K end generated high and low cytotoxic responses, respectively, to H-2D(d)-TNP. The intermediate responder and low responder status of the A.TL and A.AL strains, respectively, indicated that a gene mapping in the K region of H-2 influences response potential. Furthermore, the differences in the levels of cytotoxicity detected in the A.TH and A.TL strains suggested an additional I region influence. Taken together these findings raise the possibility that multiple genes mapping within different regions of the MHC control the level of T-cell-mediated cytotoxicity to chemically modified autologous cells.
Antibody-dependent eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: damage by purieid eosinophils.
Authors: Butterworth A E , David J R , Franks D , Mahmoud A A , David P H , Sturrock R F , Houba V
Published: June 2004

After earlier observations that antibody-dependent, cell-mediated damage to 51Cr-labeled schistosomula can be ablated by pretreatment of a mixed preparation of human peripheral blood leukocytes with an anti-eosinophil serum and complement, we investigated the cytotoxic effects of eosinophil-enriched cell preparations. Preparations containing up to 98.5% eosinophils and devoid of neutrophils were effective in mediating antibody-dependent damage to schistosomula. Preparations enriched in mononuclear cells or in neutrophils, and devoid of eosinophils, were inactive. Eosinophils from some patients with eosinophilia induced by schistosomiasis were less active on a cell-to-cell basis than cells from normal individuals. The possibility that such cells were initially blocked by immune complexes was considered, and it was found that reasonable cytotoxicity by purified eosinophils from patients with eosinophilia could be generated by overnight cultures. A possible requirement for cooperation between eosinophils and other cell types was also studied. Lymphocytes, neutrophils and monocytes failed to enhance eosinophil-mediated cytotoxicity. These results provide further evidence that the eosinophil is the only cell in man responsible for antibody-dependent, complement-independent damage to schistosomula in vitro. Eosinophils from individuals, however, differ in their cytotoxic potential by a mechanism yet to be elucidated. The possible relationship of these findings to immunity in vivo is discussed.
Detection, isolation, and functional characterization of two human T-cell subclasses bearing unique differentiation antigens.
Authors: Evans R L , Breard J M , Lazarus H , Schlossman S F , Chess L
Published: June 2004

A heterologous antihuman T-cell serum (anti-TH1), raised against purified peripheral T cells, and absorbed with an autologous Ig+ line, was shown to bind specifically to T- but not to B-lymphoid cells by both a complement-dependent cytotoxic assay and indirect immunofluorescence. Whereas 90% fetal thymocytes and thymocytes were killed by anti-TH1 and complement, a consistently restricted population (50-60%) of peripheral T cells from several normal donors were lysed, indicating that anti-TH1 is directed against one or more thymus-specific antigens which are lost or reduced on a subpopulation of human T cells in the periphery. Functional analysis of the unreactive (TH1-) and reactive (TH1+) T-cell subclasses demonstrated that TH1- cells mounted a good proliferative response to a battery of specific soluble antigens (mumps, PPD, tetanus toxoid) but neither responded in MLC, nor elaborated LMF in response to tetanus toxoid. In contrast TH1+ cells proliferated in MLC and elaborated LMF but did not respond by 3H-incorporation to soluble antigens. The relevance of these findings to human T-cell functions in vivo and to previously described functional subclasses of murine T cells is discussed.
The flow of blood to lymph nodes and its relation to lymphocyte traffic and the immune response.
Authors: Hay J B , Hobbs B B
Published: June 2004

The blood flow to individual lymph nodes of sheep and rabbits has been determined with 85Sr-labeled microspheres. A popliteal node of the sheep received 0.014% of the cardiac output and a comparable node in the rabbit 0.011%. A sheep lymph node weighing 1 g received an average of 24 ml/h of blood. It was calculated that there was a highly selective removal of lymphocytes by the node and that an equivalent to one in every four lymphocytes that entered a normal lymph node migrated out of the blood, through the substance of the node, and into the efferent lymph. During the immune response to either allogeneic lymphocytes or tuberculin, the blood flow to sheep lymph nodes, even without considering the increase in node weight, increased an average of fourfold. During the primary immune response in the rabbit to keyhole limpet hemocyanin, the blood flow increased threefold. The increase in blood flow preceded the antigen-induced increase in lymphocyte traffic recorded in the efferent lymph. The early phase of increased blood flow was considered to be due to hyperemia, whereas the latter phase had a significant angiogenesis component. It was calculated that an equivalent to 60% of the entire mobilizable pool of lymphocytes could pass through an average lymph node in the blood during an immune response lasting 5 days.