bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement.
Authors: Pangburn M K , Müller-Eberhard H J
Published: June 2004

The reaction of [14C]methylamine with native human C3 led to the stoichiometric incorporation of methylamine, loss of hemolytic activity, and the concomitant exposure of a sulfhydryl group that could be labeled with [14C]iodoacetamide. Both labeled sites were located in the C3d portion of the alpha-chain, which is known to contain the metastable binding of C3b. The methylamine-modified C3 [C3(CH3NH2)] was shown to exhibit many of the functional properties of C3b, although the C3a portion of the molecule remained covalently attached. C3(CH3NH2) bound Factor B and beta 1H, and could be cleaved by C3b inactivator in the presence of beta 1H. C3(CH3NH2) added to human serum caused activation of the alternative pathway and consumption of C3. In presence of Factors B and D and Mg++, C3(CH2NH2) formed a C3 convertase. The convertase-forming material could be removed from solution by anti-C3a Sepharose and the preformed convertase was completely inhibited by purified antibody to C3a. This antibody did not affect the function of the C3 convertase that contained C3b. Similar functional properties were exhibited by C3 exposed for short periods of time to relatively low concentrations of chaotropic reagents, such as KSCN or guanidine. These results suggest that the initial C3 convertase of the alternative pathway may be formed from native C3, without proteolysis, by the attack of a variety of nucleophiles including water. The C3 convertase formed from this altered C3 then generates by proteolytic cleavage the initial metastable C3b that is capable of attaching to receptive surfaces. Conversion of C3 to C3b exposes one sulfhydryl residue as does modification of C3 with methylamine. When the C3d portion of C3b bound to zymosan particles via the metastable binding site was treated with radiolabeled methylamine, the fragment was released from the particles in radiolabeled form. These findings are consistent with the concept that native C3 contains an active carbonyl group, probably in the form of a thioester, which can either react with water to form functionally C3b-l;ike C3 or, upon enzymatic conversion of C3 to C3b, allows C3b to form an ester bond with hydroxyl groups on the target surface.
Location of T cell and major histocompatibility complex antigens in the human thymus.
Authors: Bhan A K , Reinherz E L , Poppema S , McCluskey R T , Schlossman S F
Published: June 2004

A series of monoclonal antibodies were used to study the intrathymic distribution of T cell-specific antigens, Ia antigens, and beta 2-microglobulin in frozen sections of human thymus by immunofluorescence and immunoperoxidase techniques. Most of the cortical thymocytes reacted with anti-T4, anti-T5, anti-T6, anti-T8, and anti-T10 antibodies, thus indicating coexpression of multiple antigens on cortical lymphocytes. The staining of cells in the medulla was most satisfactorily judged in sections stained with the immunoperoxidase technique. Many medullary cells reacted with anti-T4--and a smaller fraction with anti-T5, anti-T6, anti-T8, and anti-T10 antibodies. In addition, T1 and T3 antibodies, which react with all peripheral T cells, stained a majority of medullary cells. The medullary cells were also more intensely stained with antibodies directed against beta 2-microglobulin than the majority of cortical cells. Hence, the staining profile of medulla approximates the staining pattern of peripheral T cells, with large numbers of cells bearing T1+, T3+, and T4+ antigens (helper/inducer cells) and a small number of cells bearing T1+, T3+, and T5+/T8+ antigens (suppressor/cytotoxic cells). This supports the conclusion that mature cells present in the medulla are derived from immature cells in the cortex. However, a small number of cells scattered throughout the cortex stained with T1 and T3 antibodies, which suggests that maturation of thymocytes can also occur in the cortex. Antibody directed against Ia antigens resulted in a characteristic patchy pattern of staining in the cortex and in diffuse staining in the medulla, which was interpreted as resulting from staining of epithelial reticulum. The majority of thymocytes did not stain. The staining pattern suggests a close relationship between epithelial cells and thymocytes.
Concanavalin A-inducible, interleukin-2-producing T cell hybridoma.
Authors: Harwell L , Skidmore B , Marrack P , Kappler J
Published: June 2004

The fusion of an AKR T cell tumor line to normal B6D2F1, T cells resulted in the production of a cloned T cell hybridoma (FS6-14.13) inducible with the mitogen concanavalin A (Con A). The supernate from Con A-stimulated hybridoma cells was active both in the stimulation of an anti-sheep red blood cell response by partially T cell-depleted B cells and in the stimulation of the growth of antigen-specific T cell blasts. The active principle in both assays had a molecular weight of approximately 30-40,000. These results indicated the presence of interleukin 2 (IL2) in the hybridoma supernate. The activity of the hybridoma supernate in B cell responses was dependent on the presence of adherent cells and a few contaminating T cells. On the other hand, Con A-stimulated supernates from normal spleen cells were active after either adherent cell removal or severe T cell depletion. These results suggested that IL2 was the only active helper factor in the hybridoma supernate, but that additional helper factors were present in supernates from Con A-stimulated normal spleen cells.
Human monoclonal macroglobulins with specificity for Klebsiella K polysaccharides that contain 3,4-pyruvylated-D-galactose and 4,6-pyruvylated-D-galactose.
Authors: Kabat E A , Liao J , Bretting H , Franklin E C , Geltner D , Frangione B , Koshland M E , Shyong J , Osserman E F
Published: June 2004

Two human IgM myeloma proteins, IgMWEA and IgMMAY, were found to react with agar and Klebsiella polysaccharides that contain pyruvylated D-galactose (DGal). Quantitative precipitin data and precipitin inhibition studies with methyl alpha- and beta-glycosides of 4,6-pyruvylated-D-galactose showed their combining sites to be different, although each was directed against the pyruvylated-D-Gal, one reacting most specifically with Klebsiella polysaccharides with terminal nonreducing beta-linked 2,4 pyruvylated-D-Gal, whereas the other reacted equally well with Klebsiella polysaccharides that contain 3,4 beta-linked and 4,6 alpha-linked terminal nonreducing pyruvylated-DGal. Inhibition studies showed that both sites are directed toward one of the two space isomers of 3,4- or 4,6-pyruvylated DGal, the form in which the methyl group of the pyruvate is equatorial, or endo, and its carboxyl group axial, or exo, to the plane of the acetal ring. Coprecipitation studies showed the combining site of IgMWEA to be located on an (Fab')2 fragment and not on the (Fc)5mu fragment. The monoclonal peak in the serum of IgMMAY was specifically precipitated by Klebsiella polysaccharide. Myeloma proteins with specificities of this type may occur with reasonable frequency in humans and may be a consequence of clonal expansion from inapparent infection, carrier states, or disease produced by various Klebsiella organisms.
Regulation of murine B cells through surface immunoglobulin. I. Monoclonal anti-delta antibody that induces allotype-specific proliferation.
Authors: Zitron I M , Clevinger B L
Published: June 2004

We describe the identification of a monoclonal antibody that recognizes a determinant on the delta chain of mice of the Iga, allotype groups. The monoclonal Ig in soluble form induces allotype-specific proliferation by splenic B lymphocytes from normal animals of these haplotypes. Spleen cells from mice bearing the X-linked defect of CBA/N mice fail to respond, although they bear the determinant. Proliferation is independent of T lymphocytes. The data indicate a direct triggering function for sIgD.
Epidermal proliferation of nude mouse skin, pig skin, and pig skin grafts. Failure of nude mouse skin to respond to the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate.
Authors: Krueger G G , Chambers D A , Shelby J
Published: June 2004

Human skin transplanted to nude mice offers a possible experimental system for the study of normal epidermal proliferation and differentiation, and for their pathological counterparts. Crucial to the development of such a system is the demonstration that such grafts retain the responsive features of donor skin. To document that donor proliferative characteristics are maintained in the grafts, a comparative analysis of agents that induce proliferation was made on skin of mice homozygous and heterozygous for nude, on pig skin, and on pig skin transplanted onto nude mice. A wave of epidermal proliferation could be induced in pig skin and pig skin grafted onto nude mice, but not in nude mouse skin after the topical application of 10 ng 12-O-tetradecanoyl phorbol 13-acetate (TPA). A 10-fold greater concentration of TPA or 5% croton oil induced proliferation in all species of epidermis studied. Mice, heterozygous for nude, showed a normal response to 10 ng TPA, suggesting that the ability to respond to TPA may be related, in part, to a recessive genetic trait. Nude mouse skin transplanted to a heterozygous littermate capable of responding to 10 ng TPA does not respond. These observations argue that: the graft retains its donor proliferative characteristics when transplanted to the nude, and the inability of the nude mouse to respond to lower doses of TPA may be related to absorption, the nude gene(s), or an inherent threshold to response. The lack of response to the promoter TPA provides a plausible explanation for the decreased incidence of tumors arising in nude mice during two-stage carcinogenesis experiments.
IgA proteases of two distinct specificities are released by Neisseria meningitidis.
Authors: Mulks M H , Plaut A G , Feldman H A , Frangione B
Published: June 2004

Strains of Neisseria meningitidis produce two distinct extracellular IgA proteases that cleave the human IgA1 heavy chain at different points within the hinge region. Type 1 protease cleaves the prolyl-seryl peptide bond at position 237-238; type type 2 protease cleaves the prolyl-threonyl bond two residues amino terminal to that bond attacked by type 1 enzyme. Each meningococcal isolate elaborates only one of these two enzymes, and the type of protease produced correlates with certain serogroups: group A yielding only type 1, and groups X and Y only type 2 enzyme. In addition, analysis of amino acid sequences of human alpha-chain proteins reveals that the repeating octapeptide characteristic of the IgA1 hinge region is actually triplicated.
Elicitation of delayed-type hypersensitivity responses to poly(L-Tyr,LGlu)-poly(DLAla)--poly(LLys) by anti-idiotypic antibodies.
Authors: Strassmann G , Lifshitz R , Mozes E
Published: June 2004

The in vivo effect of murine anti-idiotypic serum against C3H.SW anti-poly(LTyr,LGlu)-poly(DLAla)-(LLys) [(T,G)-A--L] antibodies on delayed type hypersensitivity responses to (T,G)-A--L was studied. Anti-idiotypic serum could challenge DTH responses in C3H.SW mice transferred with antigen-sensitized T cells. The elicitation activity was shown to be antigen and strain specific. With H-2-compatible (but allotype different) strain combinations of (T,G)-A--L-educated T cells and recipients, we were able to show that the biological effect of the anti-idiotypic serum is expressed on the first antigen-sensitized idiotype-positive radioresistant T cell, but not on the proliferating normal cells of recipient origin that participate in the efferent phase of delayed-type hypersensitivity responses to (T,G)-A--L.
Degradation of connective tissue matrices by macrophages. II. Influence of matrix composition on proteolysis of glycoproteins, elastin, and collagen by macrophages in culture.
Authors: Jones P A , Werb Z
Published: June 2004

Thioglycollate-elicited mouse peritoneal macrophages were cultured in contact with the mixture of extracellular matrix proteins produced by rat smooth muscle cells in culture. Both live macrophages and their conditioned media hydrolyzed glycoproteins, elastin, and collagen. Live macrophages also degraded extracellular connective tissue proteins secreted by endothelial cells and fibroblasts. The glycoproteins in the matrix markedly inhibited the rate of digestion of the other macromolecules, particularly elastin. When plasminogen was added to the matrix, activation of plasminogen to plasmin resulted in the hydrolysis of the glycoprotein components, which then allowed the macrophage elastase easier access to its substrate, elastin. Thus, although plasmin has no direct elastinolytic activity, its presence accelerated the rate of hydrolysis of elastin and therefore the rate of matrix degradation. These findings may be important in an understanding of disease states, such as emphysema and atherosclerosis, that are characterized by the destruction of connective tissue.
Degradation of connective tissue matrices by macrophages. III. Morphological and biochemical studies on extracellular, pericellular, and intracellular events in matrix proteolysis by macrophages in culture.
Authors: Werb Z , Bainton D F , Jones P A
Published: June 2004

We have shown that macrophages in culture degrade the glycoproteins and amorphous elastin of insoluble extracellular matrices. Ultrastructural observation of the macrophage-matrix interaction revealed that connective tissue macromolecules were solubilized from the matrix extracellularly. At least part of the matrix breakdown was localized to the immediate vicinity of the cells, as shown by morphological and biochemical studies, although the rate of degradation correlated closely with the secretion of proteinases by various inflammatory stimuli in vivo, by glucocorticoids, prostaglandin E2 or colchicine, or by phagocytosis of latex, zymosan, or cholesterol-albumin complexes in culture was reflected in altered rates of glycoprotein and elastin degradation by the macrophages. Alteration of endocytosis and lysosomal digestion by cytochalasin B, NH4Cl, and proteinase inhibitors did not decrease the overall rate of matrix solubilization, but reduced the processing of the matrix fragments to peptides. Therefore, extracellular, pericellular, and lysosomal events each contribute to degradation of extracellular matrix macromolecules by inflammatory macrophages.
Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VI. Evidence for different T cell receptors in cells that mediate H-21-restricted and H-2D-restricted cutaneous sensitivity responses.
Authors: Sunday M E , Benacerraf B , Dorf M E
Published: June 2004

We have previously shown that cross-reactive sensitivity (CS) responses induced by 4-hydroxy-3-nitrophenyl acetyl-O-succinimide (NP-O-Su) and elicited by its 5-iodo analogue, 4-hydroxy-5-iodo-3-nitrophenyl acetyl-O-succinimide were observed in strains of mice possessing the Igh-1b allotype, but not in strains bearing allotypes Igh-1c or Igh-1j. These CS responses are mediated by T cells and can be transferred to naive recipients that are homologous at either the H-2K, H-2I, or H-2D regions of the major histocompatibility complex. We now extend our analysis of cross-reactive 4-hydroxy-3-nitrophenyl-acetyl (NP)-induced CS responses to inbred strains of mice expressing additional Igh-1 allotypes. In contrast to NP-induced delayed-type hypersensitivity responses, which only display 4-hydroxy-5-iodo-3-nitrophenyl acetyl (NIP) cross-reactivity in Igh-1b-bearing mice, cross-reactive CS responses can also be elicited in NP-primed mice carrying the Igh-1d, Igh-1e, or Igh-1f allotypes. Moreover, cross-reactive NP-induced CS responses could be transferred by NP-O-Su-primed lymph node cells from the AKR (Igh-1d) strain, into naive recipients homologous at the H-2D region, but only non-cross-reactive NP responses could be transferred into strains homologous at the H-2I region. Furthermore, the lack of cross-reactivity in the Igh-1j-bearing C3H strain was not the result of an inability of these mice to recognize NP in association with H-2K/D products, because NP-O-Su-primed cells from C3H donors transferred NP-specific CS responses into both H-2D and H02I homologous recipients. The results are discussed with respect to the nature of the T cell receptors that control NP responses.
Identification of tryptic peptides unique to a 110,000-molecular weight polyprotein encoded by the T-8 isolate of murine leukemia virus.
Authors: van de Ven W J , Reynolds F H , Blomberg J , Stephenson J R
Published: June 2004

Mink cells nonproductively-infected with the weakly-transforming T-8 isolate of murine leukemia virus (MuLV) express a 110,000 mol wt polyprotein designated T-8 P110. By immunoprecipitation analysis, T-8 P110 is shown to contain AKR-MuLV amino terminal gag gene-specific components (p15, p12) but to lack p30, p10, gp70, and p15(E) antigenic determinants. These observations are further substantiated by tryptic peptide analysis indicating T-8 P110 to share approximately six lysine-containing tryptic peptides with AKR-MuLV Pr65gag, and none with AKr-MuLV Pr82env. Furthermore, of seven methionine-containing T-8 P110 tryptic peptides, at least four can be conclusively shown not to be present in either AKr-MuLV Pr180gag/pol or Pr82env. A clonal mink cell line nonproductively infected by T-8, and expressing high levels of P110, although not morphologically transformed, is shown to lack elevated levels of tyrosine-specific protein kinase activity and reduction of epidermal growth factor binding sites characteristic of cells transformed by many other RNA-transforming viruses. These findings argue either that the T-8 viral genome contains acquired cellular sequences encoding a portion of P110, or that T-8 P110 represents an inphase deletion of AKR-MuLV Pr180gag/pol with extensive posttranlational modification and that an as yet unidentified protein is responsible for T-8 associated transformation.
Sendai virus-specific, H-2-restricted cytotoxic T lymphocyte responses of nude mice grafted with allogeneic or semi-allogeneic thymus glands.
Authors: Lake J P , Andrew M E , Pierce C W , Braciale T J
Published: June 2004

The in vitro secondary cytotoxic T lymphocyte (CTL) response to Sendai virus-treated stimulator cells by primed spleen cells from thymus gland-grafted nude mice was examined. BALB/c (H-2d) nude mice grafted with allogeneic C57BL/10 (H-2b) thymus glands developed CTL responses directed exclusively to Sendai virus-infected H-2d target cells. (C57BL/6 X BALB/c)F1 nude mice grafted with thymus glands of either parent developed CTL responses preferentially against infected target cells expressing the MHC antigens present in the parental thymus graft, but also had detectable activity for infected target cells of the parental haplotype not expressed in the thymus. These results provide evidence against the concept that self recognition by MHC-restricted CTL is directed exclusively by the MCH type of the thymus.
Release of endogenous pyrogen-activating factor from concanavalin A-stimulated human lymphocytes.
Authors: Bernheim H A , Block L H , Francis L , Atkins E
Published: June 2004

Evidence is presented that the mitogen concanavalin A stimulates human lymphocytes to produce a nonpyrogenic lymphokine (LK) that is capable of activating human monocytes but not granulocytes to produce endogenous pyrogen (EP) in vitro. The potency of this preparation should facilitate further studies to purify and characterize this agent and determine its relation to other know LK. It seems likely that this factor, which we have called EP-activating factor (EPAF), plays a significant role in the development of fever in states of delayed hypersensitivity in man.
Dendritic cells induce T cell proliferation to synthetic antigens under Ir gene control.
Authors: Sunshine G H , Katz D R , Feldmann M
Published: June 2004

Dendritic cells prepared by a modification of the method of Steinman and Cohn are I-A+ and FcR-. They are extremely potent at activating not only allogeneic T cell proliferation but also antigen-specific syngeneic T cell proliferation. Dendritic cells from nonresponder strains are unable to present antigens to responder X nonresponder T cells, suggesting that they may be a site of Ir gene product expression.
Immunochemical specificity of the combining site of murine myeloma protein CAL20 TEPC1035 reactive with dextrans.
Authors: Sugii S , Kabat E A , Shapiro M , Potter M
Published: June 2004

The immunochemical specificity of the combining sites of murine myeloma protein CAL20 TEPC1035 was studied by quantitative precipitin and precipitin inhibition assays. Myeloma protein CAL20 TEPC1035 precipitated with only three dextrans, B1355S4, B1498S, and B1501S, with high proportions of alpha(1 leads to 3) linkages, but not with any other dextrans, glycogen, and pullulan. Inhibition tests with various sugars show that the combining site of myeloma protein CAL20 TEPC1035 is most complementary to panose, a trisaccharide DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 4)DGlc. Panose was 3.3 times more potent than a tetrasaccharide DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 4)DGlc alpha(1 leads to 4)DGlc and 8, 23, 42, > 42 times more active than maltose, nigerose, isomaltose, and kojibiose, respectively. These findings were paralleled by their binding properties as determined by affinity electrophoresis. The association constants (Ka) of these three dextrans to myeloma protein CAL20 TEPC1035 ranged from 3.8 X 10(3) ml/g to 5.02 X 10(3) ml/g. The association constant of inhibitor (Kia) of panose was 8.19 X 10(3) M-1. Myeloma protein CAL20 TEPC1035 is an antidextran with specificity different from those of other murine myeloma antidextrans and from human antidextrans reported previously and its combining site size is at least as large as a trisaccharide. The binding constant of methyl alpha-D-glucoside (7.2 X 10(2)) was 73% of that of panose and comparable to that of myeloma protein W3129 (9.4 X 10(2)) with a cavity-type site and 600 times lower (1.6 X 10(0)) for QUPC52 with a groove type site, indicating that the terminal nonreducing residue is held in a cavity. Inhibition data with various alpha(1 leads to 4)-linked oligosaccharides also indicate that the internal portions of these inhibitors may react directly with a portion of the combining site. These findings suggest that myeloma antidextran CAL20 TEPC1035 has a partial cavity-type combining site in which the terminal nonreducing dGlc alpha(1 leads to 6) moiety is held in a cavity with the other two sugars forming a groove. However, oligosaccharides with one or more alternating [leads to 3DGlc alpha(1 leads to 6)DGlc alpha(1 leads to 3)DGlcl leads to] units with and without terminal nonreducing DGlc alpha(1 leads to 6) or DGLc alpha(1 leads to 3) side chains remain to be tested to determine whether structures known to be present in the three dextrans which precipitate CAL20 TEPC1035 may not prove to be more active than panose.
Identification of alpha-naphthyl butyrate esterase as a plasma membrane ectoenzyme of monocytes and as a discrete intracellular membrane-bounded organelle in lymphocytes.
Authors: Bozdech M J , Bainton D F
Published: June 2004

A reaction for an esterase, with a nonhalogenated, short-chain naphthyl ester (alpha-naphthyl butyrate or alpha-naphthyl acetate) as the substrate, has been used to identify mononuclear phagocytes by light microscopy. By analyzing techniques used in the collection, separation, fixation, processing, and embedding of human blood leukocytes for electron microscopy, we adapted the light microscopic method for use in determining the fine structural localization of this reaction. In monocytes, the reaction product covered the external surface of the plasma membrane. This distribution indicated that monocytic esterase is an ectoenzyme. The addition of NaF completely inhibited the monocytic reaction. In lymphocytes, the reaction product was localized in membrane-bounded intracellular organelles, similar to those previously shown to contain phospholipid and called Gall bodies. These organelles correspond with the punctate densities or focal reaction product observed by light microscopy. Other investigators believe that this distribution of enzyme in lymphocytes marks a subset of T cells, the Tmicro. The lymphocytic reaction was not inhibited by NaF.
Distribution of T cell subsets in human lymph nodes.
Authors: Poppema S , Bhan A K , Reinherz E L , McCluskey R T , Schlossman S F
Published: June 2004

A series of T cell-specific monoclonal antibodies was used to determine the location of T lymphocyte subpopulations in frozen sections of human lymph nodes by means of an immunoperoxidase technique. The majority of cells in the paracortical regions were reactive with anti-T1 and anti-T3 antibodies, which define all mature peripheral T cells. In contrast, the majority of cells within primary follicles were unreactive with anti-T1 and anti-T3 antibodies, but were reactive with anti-Ia and anti-IgM antibodies. In addition, a substantial number of T1+, T3+ cells were found in the germinal centers of secondary follicles on the capsular side. The vast majority of T1+, T3+ cells in the paracortex and the follicles were reactive with anti-T4 antibody, which defines inducer/helper T cells. Only a minority of cells in these areas were reactive with anti-T5 and anti-T8 antibodies, which define cytotoxic/suppressor cells. No lymphocytes were stained with anti-T6 antibody, which reacts with a majority of thymocytes but not with peripheral T cells. Scattered cells in the paracortex showed staining for Ia antigen in an irregular dendritic pattern. The findings demonstrate that the major T cell population found within human lymph node bears the mature T1+, T3+, T4+ phenotype characteristic of inducer T cells. Moreover, the location of this population indicates that they play a role in the induction of B cell differentiation in vivo.
Receptors for cold-insoluble globulin (plasma fibronectin) on human monocytes.
Authors: Bevilacqua M P , Amrani D , Mosesson M W , Bianco C
Published: June 2004

This investigation focused on the role played by cold-insoluble globulin (CIg, plasma fibronectin) in monocyte function. Surface-bound CIg mediated a concentration-dependent of human blood monocytes to gelatin-coated surfaces. CIg also mediated the binding of gelatin-coated particles such as latex beads or tanned erythrocytes to surface-bound human monocytes. However, CIg did not mediate particle ingestion. Subfractionated CIg that was highly enriched in monomeric forms (zone II CIg, mol wt 190,000-235,000) was less effective than were fractions enriched in dimeric forms (zone I CIg, mol wt 450,000) in promoting monocyte attachment. Binding of CIg to a gelatin or plastic surface occurred in the absence of divalent cations, but monocyte attachment to CIg-coated surfaces required divalent cations, Mg++ being much more effective than Ca++. Cation-dependent cell attachment was reversible in that bound cells could be released by treatment with EDTA. Serum-mediated binding of monocytes to gelatin-coated plastic dishes was a result of its content of CIg because the binding activity was abolished by removal of CIg from serum, and could be restored by readdition of purified CIg. Treatment of monocytes with trypsin abolished subsequent cell attachment to CIg-gelatin surfaces or particles. Expression of certain other known monocyte membrane receptors (Fc and C3b) was markedly enhanced as a result of CIg-monocyte interaction. These several observations indicate that monocytes bear membrane receptors (termed receptor cold-insoluble globulin) for surface-bound CIg.
Mechanisms of regulation of cell-mediated immunity. VII. Suppressor T cells induced by suboptimal doses of antigen plus an I-J-specific allogeneic effect.
Authors: Bromberg J S , Benacerraf B , Greene M I
Published: June 2004

Intravenous injection of 0.01 mM 2,4,6-trinitrobenzene sulfonic acid-derivatized syngeneic lymphoid cells generates a Thy-1-positive, antigen-specific suppressor cell for contact sensitivity which requires an I-J allogeneic effect to become fully activated. It is necessary and sufficient for all allogeneic effect to be directed solely against the suppressor cell, and once activated, the cell can suppress in an H-2-unrestricted fashion. The results are discussed in the framework of entry into the suppressor pathway, the allogeneic effect as a reflection of normal physiologic processes, and the importance of I-J as a receptor and signal among cells in the suppressor pathway.
Antigen- and receptor-driven regulatory mechanisms. VII. H-2-restricted anti-idiotypic suppressor factor from efferent suppressor T cells.
Authors: Dietz M H , Sy M S , Benacerraf B , Nisonoff A , Greene M I , Germain R N
Published: June 2004

Azobenzenearsonate (ABA)-specific T cell-derived suppressor factor (TsF1) from A/J mice was used to induced second-order suppressor T cells (Ts2). Comparison of suppressor T cells induced by antigen (Ts1) with Ts2 induced by TsF1 revealed that Ts1 were afferent suppressors active only when given at the time of antigen priming, and not thereafter, whereas Ts2 could act when transferred at any time up to 1 d before antigen challenge for a delayed-type hypersensitivity response. This was true even when the recipient could be shown to be fully immune before transfer of Ts2, thus defining these cells as efferent suppressors. The anti-idiotypic specificity of the Ts2 was demonstrated by the ability of Ts to bind to idiotype (cross-reactive idiotype [CRI])-coated Petri dishes. A soluble extract from Ts2 (TsF2) was also capable of mediating efferent suppression that was functionally antigen- (ABA) specific. Comparison of TsF1 with this new factor, TsF2, revealed that both lack Ig-constant-region determinants, possess H-2-coded determinants, and show specific binding (to ABA and to CRI+-Ig, respectively). TsF1 acts in strains that differ with respect to H-2 and background genes, whereas TsF2 shows H-2- and non-H-2-linked genetic restrictions. This existence of H-2 restriction of TsF2 activity suggests that the apparent discrepancies in studies of H-2 restriction of TsF may be a result of the analysis of two separate classes of TsF, only one of which shows genetically restricted activity, thus unifying several models of suppressor cell activity.
Effect of interleukin 1 on human thymocytes and purified human T cells.
Authors: Maizel A L , Mehta S R , Ford R J , Lachman L B
Published: June 2004

Human Interleukin 1 (IL-1) purified by molecular weight fractionation, isoelectric focusing, and gel electrophoresis has been tested on human thymocytes and highly purified human T cells. IL-1 prepared in this manner could not support the long-term growth of T cells yet would augment lectin-stimulated mitogenesis. The IL-1 preparations were shown to possess the lectin-augmenting activity at dilutions containing less than 1 ng of the measurable protein. These data are in agreement with the model that IL-1 stimulates production of IL-2 from lectin-stimulated lymphocytes.
Conversion of monocytes to cells capable of anchorage-independent growth in vitro.
Authors: Lin H S , Gordon S , Chen D M , Kurtz M
Published: June 2004

We investigated the time-course involved in the conversion of mouse blood monocytes in vitro in cells capable of anchorage-independent growth. Two criteria were used to define when monocytes were fully converted to cells similar to mononuclear phagocytes present in inflammatory exudate, such as thioglycollate medium (TM)-elicited peritoneal exudate. They were the production of high levels of plasminogen activators and an ability to undergo anchorage-independent growth. Resident peritoneal macrophages were used as controls and for comparison. Our studies indicated that monocytes, but not resident peritoneal macrophages, could be converted to cells similar to TM-elicited mononuclear phagocytes after 2 d in culture.
Mast cell-mediated tumor-cell cytotoxicity. Role of the peroxidase system.
Authors: Henderson W R , Chi E Y , Jong E C , Klebanoff S J
Published: June 2004

Mast cells, when supplemented with H2O2 and iodide, are cytotoxic to mammalian tumor cells as determined by 51Cr release, and transmission and scanning electron microscopy. H2O2 at the concentration employed (10(-4) M) initiates mast cell degranulation, and mast cell granules (MCG), which contain a small amount of endogenous peroxidase activity, are toxic to tumor cells when combined with H2O2 and iodide. This toxicity is greatly increased by binding eosinophil peroxidase (EPO) to the MCG surface. Each component of the mast cell, MCG, or MCG-EPO system was required and toxicity was inhibited by the addition of the hemeprotein inhibitors azide or aminotriazole, which is compatible with a requirement for peroxidase in the cytotoxic reaction. A sequence of reactions is proposed in which mast cells, stimulated to release their granules by H2O2 generated by adjacent phagocytes, react with H2O2 and a halide to damage tumor cells. EPO release from eosinophils may contribute to this sequence of reactions, both by stimulation of H2O2-induced mast cell secretion and by combination with MCG to form a complex with augmented tumoricidal activity. These rections may play a role in the host defense against neoplasms.
A gene linked to the Igh-C locus controls the production of rheumatoid factor in the mouse.
Authors: Van Snick J L
Published: June 2004

In certain specific pathogen-free colonies, mice, upon aging, produce autoantibodies (RF) specific for the Fc portion of their IgG. In our colony, 129/Sv mice (H-2bvl; Igh-1a) have 10-20 times higher RF levels than C5BL/6 (h-2b; Igh-1b). In addition, the 129 have mainly IgA anti-IgG2a, and the B6 have mainly IgM anti-IgGl. We analyzed the genetic factors that control these differences. The high RF-producer phenotype of strain 129 was inherited as a recessive trait as indicated by the low RF levels of (129 X B6) F1 mice. About 1 of 4 129 X F1 (129 X B6) backcrosses and 1 of 10 (129 X B6) F2 mice had high RF levels, suggesting the involvement of two recessive genes in the control of this RF production. All F2 mice and all but one backcross with high IgA anti-IgG2a levels were homozygous for the Ihg-1a allele of the 129 mouse. In contrast, the B6-type RF was eight times more frequent in Igh-1bb than in Igh-1ab or Igh-1aa mice. High RF titers of either type were suppressed in Igh-1ab mice.
Induction of delayed-type hypersensitivity to azobenzenearsonate by a monoclonal anti-idiotype antibody.
Authors: Thomas W R , Morahan G , Walker I D , Miller J F
Published: June 2004

Azobenzenearsonate (ABA)-specific sensitivity was induced in A/J mice by injecting a monoclonal anti-idiotype reagent, 14A, directed against a determinant present on a minor subpopulation of immunoglobulin molecules within the anti-ABA antibodies of A/J mice. Sensitivity was transferrable by purified T cells and this was abrogated by treating the cells with 14A, rabbit anti-mouse immunoglobulin and complement, not by treatment with only the last two reagents. The transfer was restricted by the K-end of the major histocompatibility complex.
Mouse hepatitis virus type 4 (JHM strains). induced fatal central nervous system disease. I. genetic control and murine neuron as the susceptible site of disease.
Authors: Knobler R L , Haspel M V , Oldstone M B
Published: June 2004

Mouse hepatitis virus (JHM strain) type 4 induces acute encephalitis followed by death in many strains of laboratory mice. Immunohistochemical study in vivo and analysis of mouse neuronal cells in vitro both indicate that the target cells in this infection is the neuron. Further, examination of several inbred mouse strains and neuronal cells from them shows that disease expression is controlled by a single autosomal gene action at the level of the neuronal cell. Susceptibility is dominant but not H-2 linked. However, cultured neuronal cells and macrophages from SJL/J mice, which are resistant to this infection, fail to make significant amounts of infectious virus after an appropriate viral inoculation. Apparently the defect is not at the level of the virus-cell receptor, because these cells, in part, express viral antigens.
T lymphocyte-dependent B lymphocyte proliferative response to antigen. I Genetic restriction of the stimulation of B lymphocyte proliferation.
Authors: Tse H Y , Mond J J , Paul W E
Published: June 2004

For the purpose of examining more closely the interaction between T and B lymphocytes, we have developed an in vitro T lymphocyte-dependent B lymphocyte proliferation assay. Proliferation of B lymphocytes in response to antigen was found to depend on the presence of primed T lymphocytes; the B lymphocytes could be derived from nonprimed animals. It appears that these B cells were nonspecifically recruited to proliferate. This nonspecific recruitment, however, was found to be Ir-gene restricted in that B lymphocytes from B10.S mice, which are genetic nonresponders to the polymer Glu60-Ala30-Tyr10 (GAT), could not be stimulated by GAT-primed (responder X nonresponder) F1 T cells. The apparent lack of antigen specificity in the face of Ir gene-restricted T-B interaction may have important implications in our understanding of the recognition unit(s) on T lymphocytes.
Heterogeneity and specificity of cloned lines of influenza-virus specific cytotoxic T lymphocytes.
Authors: Braciale T J , Andrew M E , Braciale V L
Published: June 2004

Continuous lines of murine cytotoxic T lymphocytes (CTL) directed to type A influenza viruses have been generated in vitro by stimulation of individual CTL precursors in the presence of T cell-growth factor TCGF and syngeneic virus-infected stimulator cells. The cloned CTL lines are H-2 restricted in their target cell recognition and exhibit distinct patterns of influenza virus recognition. All CTL lines appear to be restricted in target cell recognition to either the H-2K or the H-2D end of the appropriate H-2 haplotype. Likewise, CTL lines of F1 origin are restricted in recognition exclusively to one of the parental haplotypes. All CTL lines examined express the Thy-1.2 and the Lyt-2-surface antigen markers. 4 of 11 cytotoxic lines examined also expressed detectable levels of the Lyt-1- surface antigen. These findings confirm at the clonal level previous observations on the H-2K/D restriction of virus-specific CTL and also demonstrate heterogeneity among H-2 restricted CTL both from the standpoint of viral antigen recognition and cell surface phenotype.
Expression of Lyt-1 antigen on certain murine B cell lymphomas.
Authors: Lanier L L , Warner N L , Ledbetter J A , Herzenberg L A
Published: June 2004

Although the Lyt-1 antigen has previously been considered a T cell-specific marker, recent evidence suggests that a population of Thy-1-, Lyt-1+ cells exists in normal lymphoid tissues. In this study, we have observed that the WEHI-55, WEHI-259, and CH5 B cell lymphomas express high levels of the Lyt-1 antigen, as detected by monoclonal antibodies using the fluorescence activated cell sorter. Three other B cell lymphomas of the 11 examined also gave weak but detectable reactions with the anti Lyt-1 monoclonal antibody. Except for the expression of the Lyt-1 antigen, these lymphomas are typical of cells in the B cell lineage with respect to surface phenotype. The Lyt-1 glycoprotein immunoprecipitated from metabolically labeled WEHI-55 cells is similar in structure to the Lyt-1 glycoprotein on thymocytes. These findings are similar to recent reports that B-type human lymphocytic leukemia cells express the putative human homologue of Lyt-1, the Leu-1 antigen.
Effect of helper T cells on the primary in vitro production of delayed-type hypersensitivity to influenza virus.
Authors: Leung K N , Ada G L
Published: June 2004

Injection of mice with infectious or noninfectious preparations of influenza virus induces the formation of T cells which, when added to primary tissue cultures of normal spleen cells exposed to influenza virus, enhance the generation of effector T cells which mediate delayed-type hypersensitivity (DTH) reaction. The enhancing cells possess Thy-1 and Ly-1 surface antigens are radioresistant and antigen-specific. If infectious virus was used to stimulate the DTH response in vitro, help was delivered whether homologous or heterologous A strain influenza virus was used to generate the helper T cells (Th) in vivo. In contrast, only Th cells generated using homologous virus were effective if noninfectious virus was used to stimulate the DTH response in vitro. Peak helper activity occurred 2 d after virus injection and the Th cells were only effective if added to the primary cultures within 24 h after addition of the stimulating antigen. The Th cells enhanced the generation of both classes of DTH effector cells, i.e., those that are Ly-1 positive and IA-subregion restricted and those that are Ly-2,3 positive and K,D-region restricted. The activity of the Th cells was found to be IA-subregion restricted and this was shown to operate at the level of the stimulator cells so that the delivery of help to the responder cells was not H-2 restricted. The possibility that the Th cells might be a precursor to the Ly-1 positive IA subregion-restricted DTH effector cells is discussed.
Influence of Igh-linked gene products on the generation of T helper cells in the response to sheep erythrocytes.
Authors: Nutt N , Haber J , Wortis H H
Published: June 2004

The role of Igh-linked loci in the generation and expression of T cell help for antibody responses to sheep erythrocytes (SRBC) was investigated. The production of IgM, IgG3, IgG1, IgG2b, and IgG2a antibody to SRBC was shown to be T cell dependent. The Igh-congenic mouse pair CBA/Tufts (Ighj) and CBA.Ighb gave equivalent responses to SRBC. CBA.nude mice (Ighj) supplemented with peripheral T cells of either Ighj or Ighb genotype produced equivalent, high responses. Therefore, T cell-B cell mismatching for the Igh haplotype is not in itself a bar to the generation or expression of help. In contrast, T cells primed in an environment that lacks Ighj-linked products are inefficient helpers for Ighj B cells. These results suggest that antigen-primed B cells or their products prime a set of T cells that can help B cells that bear matching, Igh-linked gene products.
Interactions between lymphocyte membrane molecules. I. Interaction between B lymphocyte surface IgM and Fc IgG receptors requires ligand occupancy of both receptors.
Authors: Dickler H B , Kubicek M T
Published: June 2004

The independent B lymphocyte surface membrane receptors IgM and Fc IgG receptors were evaluated for interactions using immunoflourescence. Ligand [F(ab')2 anti-mu]-induced capping of surface IgM resulted in capping of Fc IgG receptors only if the latter were occupied during the capping process by: (a) soluble antigen-antibody complexes that themselves provided insufficient cross-linking to result in capping; or (b) monomeric IgG at physiologic concentrations (or less) either purified or as normal serum. Ligand-induced capping of Fc IgG receptors did not result in capping of surface IgM occupied by monomeric F(ab') anti-mu. Control experiments showed that ligand binding to or capping of only one of these two receptors has no effect on the other, and that there were no cross-reactions. The interaction appears specific in that ligand-induced capping of surface IgM did not induce capping of ligand-occupied surface IgD or I-A antigens. Thus, there appears to be a specific interaction between ligand-bound surface IgM and ligand-bound Fc IgG receptors on the B lymphocyte surface. The results also indicate that binding of monomeric IgG produces a reversible alteration in the Fc IgG receptor leading to association with ligand-bound surface IgM. Because Fc IgG receptors are continuously exposed to monomeric IgG in vivo, these results suggest that whenever surface IgM is involved in a B lymphocyte response to an immunologic stimulus, the Fc IgG receptor is also involved.
T cell growth factor abrogates concanavalin A-induced suppressor cell function
Authors: Palacios R , Moller G
Published: June 2004

Concanavalin A (Con-A)-induced suppressor T cells were found to respond to T cell growth factor (TCGF) by proliferation. TCGF abrogated the suppressor activity exerted by these cells on phytohemagglutinin (PHA)- and alloantigen- induced lymphocyte proliferation and on pokeweed mitogen (PWM)-driven immunoglobulin secretion. The Con-A-activated suppressor T cells absorbed the TCGF activity, preincubation of these active suppressor cells with TCGF abolished their suppressor activity and addition of increasing numbers of Con-A-activated T cells reverted the abrogator,/ effect of TCGF. Altogether, these findings suggest that Con-A-induced suppressor T cells exert their function by decreasing the available levels of TCGF. Cyclosporin-A (CYA), which is known to inhibit the expression of receptors for TCGF on T cells, also inhibited the suppressor activity as determined in both indicator systems, namely PHA- or alloantigen-induced DNA synthesis and PWM-induced immunoglobulin synthesis. CYA made Con-A-treated T cells unresponsive to TCGF and unable to absorb the growth factor, supporting the notion that CYA inhibits the expression of TCGF receptors on T cells, a mechanism by which this drug seems to abrogate Con-A-induced suppressor T cell function.
Nucleic acid and protein sequences of phosphocholine-binding light chains.
Authors: Kwan S P , Rudikoff S , Seidman J G , Leder P , Scharff M D
Published: June 2004

An 18-kilobase DNA fragment containing the sequence coding for both the variable and constant regions of the S107 mouse immunoglobulin light chain was cloned from total cellular DNA. The complete nucleotide sequence of the kappa-chain variable-region gene is reported. Determination of the amino acid sequence encoded by the DNA is found to be identical to the protein sequence of the T15 light chain through residue 88. Direct sequence analysis confirmed that the J1 joining segment is used in the recombination event producing the active kappa light chain gene.
Chemotactic activity generated from the fifth component of complement by plasma kallikrein of the rabbit.
Authors: Wiggins R C , Giclas P C , Henson P M
Published: June 2004

Rabbit plasma kallikrein incubated with rabbit C5 resulted in the generation of chemotactic and secretagogue activity for rabbit neutrophils. This effect on C5 appeared to be due to kallikrein itself and not to a contaminating enzyme, because it could be inhibited by anti-kallikrein IgG or by soybean trypsin inhibitor to the same extent the kinin generation by the same kallikrein preparation was inhibited by these agents. The chemotactic response was consistent with the generation of a C5a-like peptide from C5 because the effect could be partially inhibited by carboxypeptidase N and was related to the generation of a small (approximately 14,000 mol wt) fragment of C5. No direct chemotactic response was detectable for kallikrein, activated Hageman factor, high-molecular weight kininogen, or intact C5. Incubation of Kallikrein, high-molecular weight kininogen, and Hageman factor together, so that activation of all three proteins occurred, did not results in the generation of detectable chemotactic activity.