bluuebunny/crossref_metadata_2025 huggingface dataset:
The biochemical characterization of a cell surface antigen associated with acute lymphoblastic leukemia and lymphocyte precursors.
Authors: Newman R A , Sutherland R , Greaves M F
Published: December 2022

The acute lymphoblastic leukemia- (ALL) associated membrane antigen is a single glycosylated polypeptide of approximate m.w. of 100,000 (gp100), containing no intrachain disulfide linkages. Approximately 50% of gp100 will bind to lentil lectin, whereas 100% will bind to the lectin from Ricinus communis. Both lentil-binding and lentil nonbinding forms of the antigen appear to be identical by 2-dimensional isoelectric focusing/SDS polyacrylamide gel electrophoresis and peptide mapping. Carbohydrate, although contributing approximately 20 to 25% of the m.w., appears not to be involved in the antigenic site of the ALL antigen as judged by precipitation of a molecule after tunicamycin treatment of cells or glycosidase digestion. Charge shift electrophoresis and labeling with the lipophilic nitrene reagent hexanoyl diiodo-N-(4-azido-2-nitrophenyl)-tyramine suggests that the cALL antigen is probably not an integral membrane protein; however, it remains tightly bound to the plasma membrane after subcellular fractionation. A glycoprotein of the same m.w. has been detected by immunoprecipitation on bone marrow cells of nonleukemic patients. serologic studies indicate that the cALL-associated antigen is found on the terminal transferase-positive lymphoid cells, and it therefore seems likely that the gp100 molecule is a normal gene products of lymphocyte precursors.
Qualitative and quantitative assessment of C3-receptor reactivities on lymphoid and phagocytic cells.
Authors: Schmitt M , Mussel H H , Dierich M P
Published: December 2022

Highly purified human C3, free of C5 and beta 1H, was used to prepare EAC14oxy23b, EAC14oxy23b' (C3b cells treated with purified C3bINA and beta 1H) and EAC14oxy23d (C3b' cells treated with trypsin). These intermediates were used to assess by rosette formation C3-receptor activity on various cells. The number of cell-bound C3 per C3b, C3b', and C3d cell was quantified by applying 14C-formaldehyde-labeled C3. Human PBL reacted to about the same degree with C3b, C3b', and C3d cells, whereas monocyte-free PBL enriched for B cells interacted preferentially with the C3b' and the C3d cells; human tonsil lymphocytes behaved similarly. The reaction of Raji cells was clearly assessable with C3b cells and was accelerated with C3b' and C3d cells. Daudi cells reacted with C3b' and C3d cells only, in comparison to Raji cells with a much lower activity. Human granulocytes reacted equally well with C3b and C3b' cells, but towards C3d cells they were almost unreactive. Human monocytes formed rosettes with C3b cells, and at a lower level, rosettes with C3b' cells. C3d cells were unreactive. Similar reaction patterns were obtained with guinea pig leukocytes, whereas mouse leukocytes were totally different, since peritoneal macrophages only formed rosettes with human C3b' cells.
Analysis of T lymphocyte subsets in cytomegalovirus mononucleosis.
Authors: Carney W P , Rubin R H , Hoffman R A , Hansen W P , Healey K , Hirsch M S
Published: December 2022

Lymphocyte proliferative responses to mitogens and herpes virus antigens are diminished during cytomegalovirus (CMV) mononucleosis. We analyzed peripheral blood T lymphocytes from patients in the acute and convalescent phases of CMV mononucleosis using monoclonal antibodies directed against the T helper and the T cytotoxic-suppressor cell subsets. Acute CMV infection is associated with a reversal in the normal ratio of helper to suppressor T lymphocytes with relative and absolute decreases in T helper cells and corresponding increases in T suppressor cells. These alterations in T lymphocyte subsets are accompanied by diminished lymphocyte responses to the mitogen concanavalin A (Con A). During convalescence, helper T lymphocytes increase, suppressor T lymphocytes decrease, and Con A responses return to normal.
Time-dependent inhibition of tuberculin-induced lymphocyte DNA synthesis by a serine protease inhibitor.
Authors: Ku G S , Quigley J P , Sultzer B M
Published: December 2022

Diisopropylfluorophosphate (DFP), a group-specific irreversible inhibitor of serine proteases, has been shown to exert time-dependent inhibition of DNA synthesis of lymphocytes stimulated by three different B lymphocyte mitogens: purified protein derivative of tuberculin (PPD), endotoxin protein (EP), and lipopolysaccharide (LPS). The time-dependent inhibition profile found in B lymphocytes is absent in concanavalin A (Con A)-stimulated T lymphocytes. Structural analogs of DFP, which have lost the phosphorylating ability, are not inhibitory. Inhibition of DNA synthesis by DFP is reversible in the first 8 hr of mitogenic stimulation. Maximal and irreversible inhibition by DFP occurs around the 16th hour of stimulation. These data support the postulate that a mitogenesis-linked protease, or proteases, in B lymphocytes is absent in the resting cells but is made available several hours before the initiation of DNA synthesis in the late G1 phase of the cell cycle.
Radiation sensitivity of human natural killer cell activity: control by X-linked genes.
Authors: Brovall C , Schacter B
Published: December 2022

The sensitivity of human natural killer cell activity after exposure of peripheral blood mononuclear cells to different doses of gamma irradiation was examined in a group of healthy adults and several families. Three patterns of radiation sensitivity were observed: 1) loss of all NK activity after 3000 rads irradiation; 2) loss of approximately 50% of the NK activity; and 3) maintenance of activity after this dose of irradiation. Low dose irradiation (500 to 2000 rads) resulted in an enhancement of activity. The radiation dose giving low dose activation reflected the individual's sensitivity to 3000 rads. Population studies and the segregation in two informative families indicate that radiation sensitivity of NK activity is controlled by X-linked codominant gene.
Lymphoid cell responses to bacterial cell wall components: mitogenic responses of murine B cells to Streptococcus mutans carbohydrate antigens.
Authors: Hamada S , McGhee J R , Kiyono H , Torii M , Michalek S M
Published: December 2022

The mitogenic activity of various purified serotype carbohydrate and cell wall lysate fractions of Streptococcus mutans for murine lymphocytes has been determined. The highest mitogenic responses occurred after 48 hr of stimulation with these carbohydrate preparations when tested on splenic cultures derived from C3H/HeJ and BALB/c mice. The response pattern obtained with optimum concentrations of these preparations was very similar to that seen with the B cell mitogen, LPS. A purified serotype g carbohydrate (M1 g) prepared by mutanolysin enzyme treatment of S. mutans 6715 cell walls stimulated good mitogenic responses in BALB/c nude and nu/+ splenic cultures, suggesting an effect on mouse B cells. This was further substantiated by studies showing that this antigen also induced responses in cultures of B cells purified by nylon wool fractionation, whereas purified T cells did not respond. Mitogenic responses were due to the carbohydrate moiety and not to possible LPS contamination, since alkaline treatment or mixture with polymyxin B greatly reduced responses to LPS; however, no alteration of mitogenic responses to M1 g occurred. Further, LPS nonresponsive C3H/HeJ spleen cells yielded good mitogenic responses to M1 g. On the other hand, periodate treatment, which is known to decompose carbohydrate moieties completely abrogated the mitogenic activity of M1 g antigen. Additional studies with serotypes c and e carbohydrate, which also induced mitogenic responses, suggested that this activity for lymphoid cells may be a common property of S. mutans cell wall carbohydrate.
Significance of class 1 and class 2 major histocompatibility complex antigens: help to allogeneic K and D antigens does not involve I recognition.
Authors: Swain S L
Published: December 2022

The significance of the dichotomy of MHC antigens was investigated. It was determined that primed helpers directed against allogeneic class 1 antigens (K and D in the mouse) were not restricted to syngeneic class 2 antigens (I in the mouse). Furthermore, the generation of helper T cell-replacing factor by stimulation with K or D antigens was not blocked by Ia antibodies that were effective in blocking the same factors generated in response to I region MHC antigens. It is concluded that class 2 antigens are not recognized during the response of helpers to class 1 antigens, and it is suggested that class 1 and class 2 molecules can perform reciprocal functions.
Immunologic control of the ascites form of murine adenocarcinoma 755. IV. Characterization of the protective antibody in hyperimmune serum.
Authors: Matthews T J , Collins J J , Roloson G J , Thiel H J , Bolognesi D P
Published: December 2022

The potent capacity of B6 anti-AD755a tumor cell serum to protect mice against challenge with large doses of the homologous tumor cells has been shown to reside in the IgG2a antibody subclass. Despite their inability to protect in vivo, other IgG subclass antibodies obtained from the anti-AD755a serum demonstrated serologic reactivities in vitro comparable to those obtained with the protective IgG2a fraction. The specificity of serum protection is linked to the oncornavirus associated with the AD755a tumor and the serum immunoprecipitates only virus structural proteins from the tumor cell surface. Removal of these antibodies by specific immunoadsorbent resins eliminated nearly all of the in vitro serologic reactivity of unfractionated serum and the IgG2a subclass, but it had absolutely no effect on their protective capacity in vivo. Further target cell-binding studies suggest that nonprotective antibodies in the anti-AD755a serum bind more efficiently to the target cell in vitro than the protective fraction and have raised the possibility that the latter antibodies may only have weak affinity for the target cell itself.
A new minor histocompatibility locus linked to H-3.
Authors: Click R E , Schneider D , Roopenian D C
Published: December 2022

B10, BALB.B, and A.BY shared an allele at a new locus not shared by B10.LP-H-3b. This locus is linked to the minor histocompatibility gene, H-3, in the 5th linkage group of chromosome 2 of the mouse. The product of the new gene fits the criteria of a minor histocompatibility antigen, since it induced as well as served as a target for cytotoxic lymphocytes (CTL) and its presence accelerated skin graft rejection when compared with that caused by H-3.1. F1 complementation of skin graft rejection and generation of CTL indicated that A.BY and BALB.B do not share H-3a with B10 as previously reported but possess the c allele of their congenic partners A and BALB/c. Thus, B10.LP-H-3b and B10 differ from one another by at least 2 minor histocompatibility loci. The specificity of CTL developed in B10. LP-H-3b and appropriate F1 hybrids indicate that the lytic activity of CTL specific for H-3.1 was restricted to target cells possessing H-2Kb antigens; this contrasted to the H-2Db-restricted activity of CTL specific for the product of the new gene.
Glycolipids of murine lymphocyte subpopulations: a defect in the levels of sialidase-sensitive sialosylated asialo GM1 in beige mouse lymphocytes.
Authors: Schwarting G A , Gajewski A
Published: December 2022

Neutral glycosphingolipids as well as some of the sialic acid containing glycolipids, or gangliosides, were quantitated from thymocytes and splenic T lymphocyte preparations from normal and natural killer-deficient mice of various ages. Previously, asialo GM1 was considered the product of acid hydrolysis of the ganglioside GM1. However, in the murine lymphoid system asialo GM1 is a normally occurring glycolipid that appears to be one of the intermediates in the biosynthesis between lactosylceramide and some recently described, terminally sialosylated gangliosides (for structures see Table I). Asialo GM1, which is a putative marker for murine natural killer cells, is unaltered in thymocytes but is found at reduced levels in 5- to 15-wk-old beige mouse splenic T cell preparations. A sialosylated derivative of asialo GM1, which is sialidase sensitive, is increased in postnatal splenic lymphocytes but then falls to below normal levels in 5- to 15-wk-old beige mice. The concentration of this ganglioside is also altered in the same manner in the thymus. Analysis of the total gangliosides of beige thymus and spleen indicates that there are several possible deletions, but it still not known whether these deletions are related to the natural killer dysfunction in these mice. These studies show that there is a defect in the synthesis or degradation of several related glycosphingolipids in beige lymphocytes, at least 1 of which contains sialic acid, but whose structure remains unknown.
Analysis of the biosynthesis of HLA-DR glycoproteins in human malignant melanoma cell lines.
Authors: Lloyd K O , Ng J , Dippold W G
Published: December 2022

Human malignant melanoma cell line SK-MEL-37 expresses HLA-DR antigens having a characteristic 2-chain structure, with heavy chains (alpha) of approximately 32,000 daltons and light chains (beta) of approximately 28,000 daltons. Nonequilibrium pH-gradient electrophoresis (NEPHGE) on HLA-DR immunoprecipitated by rabbit anti-HLA-DR sera from [35S]-methionine-labeled, pulse-chased cells showed 2 closely spaced heavy-chain components (1, 2) and 4 light-chain spots (3-6). From nonchased samples, numerous more-basic components running in the heavy chain region were also precipitated. In particular, a very basic, 30,000 dalton component (pl approximately 8.5) was prominent (component 7); this spot probably corresponds to the invariant (Ii) peptide previously demonstrated in lymphoid cell HLA-DR precipitates (9) and the M-1 peptide of Shackelford and Strominger (10). None of these components (alpha, beta, or component 7) was precipitated from extracts of HLA-DR-negative melanoma cells. Pulse-chase experiments and the use of different labeled sugar precursors showed that component 7 is a partially glycosylated intracellular precursor, possibly of the HLA-DR alpha-chain. None of the immunoprecipitates, even from cells pulse-labeled for only 15 min, contained a peptide migrating in the 55,000 to 60,000 m.w. region. It was concluded that melanoma HLA-DR is not synthesized via a polyprotein precursor. In contrast to these results, obtained with rabbit anti-HLA-DR sera, a mouse monoclonal anti-HLA-DR was found to precipitate only biosynthetically completed alpha (1, 2) and beta (3-6) chains.
Fifth component of guinea pig complement: purification and characterization.
Authors: Kinoshita T , Hong K , Kondo K , Inoue K
Published: December 2022

The 5th component of complement (C5) was purified from guinea pig serum. The 6-step procedure, involving removal of C1 by precipitation at pH 7.5, mu = 0.04, 2.0 M ammonium sulfate precipitation, acid precipitation at pH 5.6 mu = 0.1, and successive chromatographies on Sephadex G-200, DEAE-cellulose, and hydroxylapatite columns, yielded 1.6 to 4 mg of C5 from 250 ml of serum. Purified C5 gave 1 protein band on disc polyacrylamide gel electrophoresis (PAGE) and sodium dodecylsulfate-(SDS) PAGE. Guinea pig C5, like human C5, consisted of 2 polypeptide chains designated as alpha (m.w. of 108,000) and beta (m.w. of 79,000) linked together by disulfide bonds. The amino acid composition was also very similar to that of human C5. The amino-terminus of the alpha-chain was aspartic acid or asparagine, and that of the beta-chain was undetectable by the dansyl method. Limited proteolysis of C5 with trypsin caused virtually no alteration in its mobility on immunoelectrophoresis and SDS-PAGE without reduction. Cleavage with trypsin was restricted to the alpha-chain: the beta-chain was totally resistant to the digestion. The alpha-chain was split into at least 4 fragments of 58,000, 34,000, 29,000, and 27,000 daltons linked to one another and/or to the beta-chain by disulfide bonds.
The regulation of growth and differentiation of a murine B cell lymphoma. II. The inhibition of WEHI 231 by anti-immunoglobulin antibodies.
Authors: Boyd A W , Schrader J W
Published: December 2022

WEHI 231 is a murine B cell lymphoma, which from our previous studies is highly susceptible to a lipopolysaccharide (LPS) induced differentiation signal. In this paper we show that anti-immunoglobulin (Ig) antibody at low concentrations (0.1 micrograms/ml) inhibits cell proliferation and results in cell death. Heterologous sera specific for mu- and kappa-chains, and a monoclonal antibody (E4) developed in our laboratory and specific for mu-chain, profoundly suppressed the growth of WEHI 231 in both soft agar culture and liquid culture. The F(ab')2 fragments were as potent as intact Ig, indicating that neither Fc receptor binding nor complement activation were required for this inhibition of growth. Neither heterologous antibodies that bound to WEHI 231 but not to the Ig receptor, nor a monoclonal antibody that bound to non-Ig cell surface structures (a brain-associated antigen) inhibited the growth of WEHI 231. LPS did not prevent inhibition of growth by anti-Ig antibody, and even when addition of LPS preceded the addition of anti-Ig, profound inhibition occurred. WEHI 231 thus promises to be a convenient tool for investigating the mechanism of signal transmission by the Ig receptor.
Monoclonal antibodies to two determinants of melanoma-antigen p97 act synergistically in complement-dependent cytotoxicity.
Authors: Hellström I , Brown J P , Hellström K E
Published: December 2022

Microcytotoxicity tests were used to study complement-dependent cytotoxicity of 2 monoclonal IgG2a antibodies, 96.5 and 118.1, both alone and in combination. These antibodies are specific for 2 antigenic determinants, p97a and p97b, respectively, of p97, a cell-surface glycoprotein present on most human melanomas and, in smaller amounts, on other tumors and normal tissues. For 10 of 12 melanoma lines, complement-dependent cytotoxicity was much greater in the presence of both antibodies than with either antibody alone. Synergism was not observed when the antibodies were tested in combination with an IgG2a antibody to a different cell-surface glycoprotein, nor was it detected in tests of 4 non-melanoma cell lines.
Suppression of antibody responses by cells from mice treated with picryl sulfonic acid: T cells that suppress IgG antibody without inhibiting concomitant IgE responses.
Authors: Thomas W R , Watkins M C , Cox K O , Asherson G L
Published: December 2022

T cells from mice injected with picryl sulfonic acid (PSA) can inhibit the anti-trinitrophenyl (TNP) antibody responses of mice produced after skin painting with picryl chloride (PCl). This had unusual specificity because the cells could inhibit IgG PFC responses in draining lymph nodes by 90% without affecting anti-TNP IgE responses as measured by heterologous adoptive cutaneous anaphylaxis. Although showing specificity for the class of antibody, the suppressors did inhibit IgG antibody responses to another sensitizer, oxazolone, although to a lesser degree. Responses to TNP-KLH, however, were unaffected.
Human lymphocytes can generate thymus-independent as well as thymus-dependent anti-hapten plaque-forming cell responses in vitro.
Authors: Golding B , Chang S P , Golding H , Jones R E , Pratt K L , Burger D R , Rittenberg M B
Published: December 2022

Human lymphocytes from peripheral blood, tonsils, and adenoids produced hapten-specific anti-TNP antibodies after in vitro stimulation with TNP-Ba. This antigen did not appear to behave as a polyclonal activator since TNP-Ba-stimulated cells lysed TNP-conjugated sheep erythrocytes (SRBC) but not unconjugated SRBC or DPPC-conjugated SRBC, whereas cells from PWM-stimulated cultures formed hemolytic plaques with both haptenated and unhaptenated targets. In addition, TNP-Ba generated PFC were inhibitable by soluble hapten (TNP-EACA or TNP-BSA). B cells depleted of T cells (less than 1% E-RFC cells) were able to respond to TNP-Ba but not to PWM or TNP-KLH. When varying ratios of T and B cells were added to cultures the TNP-Ba anti-TNP response was found to have a linear correlation with the number of B cells added (r = 0.987) and was maximal in the absence of added T cells. This was in contrast to the response to TNP-KLH, which required T cells at a particular T:B ratio for optimal induction of anti-TNP PFC. Thus, both T-dependent and T-independent anti-hapten responses could be elicited in human lymphoid cell cultures.
Antigenic changes produced by complex formation between thrombin and antithrombin-III.
Authors: McDuffie F C , Peterson J M , Clark G , Mann K G
Published: December 2022

Immunization of goats and mules with human thrombin resulted in an antiserum that reacted only weakly with the parent molecule, prothrombin. Some of the antibodies in this antiserum showed a greater affinity for thrombin complexed to its naturally occurring inhibitor, antithrombin-III, than for active thrombin. An antiserum against the human thrombin inhibitor, antithrombin-III, produced 2 precipitin lines against human serum but only 1 against plasma. The 2nd line in serum was shown to represent precipitation of a complex of thrombin with antithrombin-III. The neoantigens appearing in antithrombin-III after complex formation were also present in complexes prepared with purified clotting factor Xa and antithrombin-III. Since purified host (mule) thrombin was also capable of causing formation of the neoantigenic sites when complexed to human antithrombin-III, it seems likely that these determinants result from interaction in the host between the immunogens (either human thrombin or antithrombin) and the appropriate interacting host protein (mule antithrombin-III or thrombin, respectively). Studies by radioimmunoassay showed that the antibodies formed are not completely specific for the neoantigens since they also react to a lesser extent with the free proteins.
Correspondence between lectin-defined and surface antigen-defined cell subpopulations in the human thymus: its variation during ontogeny.
Authors: Richard Y , Boumsell L , Coppin H , Mishall Z , Lemerle J , Bernard A
Published: December 2022

In the thymus of children, congruent to 50% of cells are recognized both by peanut agglutinin and soybean agglutinin (PNA+, SBA+), congruent to 23% of cells are PNA-, SBA-, and 23% are PNA-, SBA+. This pattern of recognition was compared with the reactivity of these cells with monoclonal antibodies recognizing T cell differentiation antigens A 50 and a series (T3, T6, T8) that defines 3 discrete stages of T cell differentiation. Most PNA+, SBA+ display T6 and T8 but not T3 antigens; most PNA-, SBA+ display T3+ and A 50+ but not T6; and T3-, T6-, A 50- cells are PNA-, SBA-. Thus, there is a close correspondence between PNA+, SBA+ cells and the common (cortical) T3-, T6+ thymocytes; between PNA-, SBA+ cells and late (medullary) T3+, T6- thymocytes; and between PNA-, SBA- cells and early thymocytes. During ontogeny, although there are fewer PNA+ cells in the thymus, the proportion of T3+ cells, T6+ cells, and T3-, T6- cells showed no major modification as early as 16 wk.
Isolation of Epstein Barr-virus and studies of its neutralization by human IgG and complement.
Authors: Nemerow G R , Cooper N R
Published: December 2022

An isolation procedure for Epstein-Barr virus (EBV) that yields substantial quantities of purified infectious virus is described. The transforming strain of EBV was obtained from the marmoset lymphoma cell line B95-8 after stimulation with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Purification was achieved by dextran density gradient ultracentrifugation in the presence of bacitracin, which was included to prevent viral aggregation. When assayed in cord blood leukocytes, isolated EBV stimulated DNA synthesis and induced the formation of colonies of transformed cells. The yield of infectious virus as determined by these assays was 13 to 29%. Electron microscopic (EM) examination of negatively stained virions revealed the presence of 115-nm spherical enveloped particles containing an internal 55-nm ring-shaped nucleoid. Interactions between 3H-thymidine labeled EBV, IgG and complement (C) were examined by rate zonal ultracentrifugation. High concentrations of immune IgG aggregated the virus whereas IgG together with C induced lysis as demonstrated by release of labeled EBV nucleic acid. EM studies of the IgG and C mixtures performed in parallel revealed accumulation of protein on the viral envelope, progressive separation of the envelope from the nucleocapsid, and disintegration of the nucleoid. Approximately 25-fold less IgG was required for neutralization than for viral aggregation. Although C did not enhance the IgG dependent neutralization, physiologic concentrations of C in normal nonimmune human serum also inactivated the virus.
Natural killer (NK) cell activity in the rat. I. Isolation and characterization of the effector cells.
Authors: Reynolds C W , Timonen T , Herberman R B
Published: December 2022

This study has demonstrated the presence of large granular lymphocytes (LGL) in the rat and implicated a central role for these cells in mediating natural killer (NK) cell activity in this species. The LGL frequency from various organs was shown to be: peripheral blood = lung greater than spleen greater than peritoneal exudate greater than lymph node. Little or no LGL were found in the thymus or bone marrow. This pattern was similar to the distribution of NK activity, except for the lungs, which had no detectable activity. These studies have also shown that discontinuous Percoll density gradients can be used to highly enrich or deplete LGL from both spleen and peripheral blood. Enriched LGL populations were shown to bind selectively to NK-susceptible target cells and to demonstrate very high NK cell cytolysis. Since human NK activity has also been found to be clearly associated with LGL, the present findings indicate that rats may provide a very useful animal model for detailed studies of the ontogeny, regulation, and in vivo relevance of NK cells.
Secretory component-dependent hepatic transport of IgA antibody-antigen complexes.
Authors: Socken D J , Simms E S , Nagy B R , Fisher M M , Underdown B J
Published: December 2022

The ability of the liver to transport antigen-antibody complexes containing polymeric IgA was tested in a model system using the isolated perfused rat liver and soluble complexes formed between trinitrophenylated (TNP) antigens and MOPC 315, a polymeric mouse IgA protein with anti-TNP activity. A double-label strategy (125I and 131I) was used to separately follow antigen and antibody during isolation and transport by the isolated perfused liver. Complexes formed in antigen excess and isolated by gel filtration were added to the perfusate. The quantity of antigen or antibody transported was determined by counting the radioactivity in collected bile fractions. TNP-human albumin (TNP-HSA) complexed to polymeric IgA antibody was transported from blood to bile while the same antigen complexed to IgG antibody was not. The transport of IgA-(TNP-HSA) complexes was inhibited by preincubation with human secretory component (SC), which indicated that transport of such complexes proceeds though an SC-dependent mechanism previously described for uncomplexed polymeric IgA antibody. Complexes (m.w. congruent to 970,000) of trinitrophenylated bovine thyroglobulin (TNP-TG) and polymeric IgA were transported less well than IgA-(TNP-HSA) complexes (m.w. less than or equal to 460,000), even though both types of complexes bound SC. The possibility that the poor transport of IgA-(TNP-TG) complexes reflected a size restriction on hepatic transport from blood to bile is discussed.
Biologic and molecular characterization of the IgG serum blocking factor (SBF-IgG) isolated from sera of patients with EBV-induced infectious mononucleosis.
Authors: Veltri R W , Kikta V A , Wainwright W H , Sprinkle P M
Published: December 2022

Our laboratory has previously reported the isolation of a serum blocking factor (SBF) from infectious mononucleosis (IM) patients. The SBF has been purified by a combination of Sephadex QAE-50 ion exchange and Sephadex G-200 molecular sieve chromatography. This material was found to be devoid of soluble immune complexes, and immunochemically and biochemically was characterized as IgG and, hence, termed SBF-IgG. The SBF-IgG was shown to significantly (alpha = 0.05) suppress antigen specific (Influenza A-1[H1N1]) in vitro lymphocyte stimulation (LS) as well as leukocyte migration-inhibition (LMI) reactivity. Also, the SBF-IgG significantly suppressed the in vitro.LS response to phytohemagglutinin. In addition, the SBF-IgG when bound to normal donor lymphocytes significantly reduced the high affinity E-rosette (HAR) reactivity at 29 degrees C. A purified T lymphocyte subpopulation of normal donor lymphocytes specifically bound SBF-IgG, and the latter could be r covered using glycine-HCI. It appears that SBF-IgG is a nonspecific antibody; it binds neither lymphokines nor specific antigen, but apparently elicits its in vitro vitro cell-mediated suppressive effect at the level of the T lymphocytes.
Control of latent allotype expression by rabbit splenocytes.
Authors: McCartney-Francis N , Mandy W J
Published: December 2022

Serologic and chemical studies have suggested that immunoglobulin structural genes are under nonallelic genetic control. The transient appearance of unexpected (i.e., latent) allotypes in serum further suggests that cellular control mechanisms may be operative. We report here the results of our efforts to induce the expression of latent allotypes by cultured rabbit splenocytes. The protein A plaque assay facilitated with various anti-allotypic antisera was used to enumerate allotype-specific plaque-forming cells. When splenocytes from a b4 b4 rabbit are cultured in the presence of anti-b4 alloantisera, the number of b4 PFC (i.e., nominal) is suppressed and the number of PFC expressing the latent allotype is increased. The specificity of the induced latent PFC is dependent upon the source and allotypic mosaic of the antiserum added to the cultures. Our results suggest that lymphocytes committed to latent allotypes are normally suppressed. Activation by the appropriate alloantiserum directed against the nominal allotype may relieve a cell-mediated suppressive mechanism.
The presence of platelet-activating factor (PAF) in normal human mixed saliva.
Authors: Cox C P , Wardlow M L , Jorgensen R , Farr R S
Published: December 2022

This report describes PAF activity in normal human mixed saliva from each of 24 randomly selected donors. The human salivary PAF (HS-PAF) was similar to rabbit basophil PAF (acetyl glyceryl ether phosphorylcholine or AGEPC) with respect to the following characteristics: 1. HS-PAF co-chromatographed with the standard rabbit basophil AGEPC and with synthetic AGEPC. 2. HS-PAF and AGEPC were unaffected by hirudin, indomethacin, and creatine phosphate/creatine phosphokinase, the respective inhibitors of platelet activation induced by thrombin, arachidonic acid, and ADP. 3. HS-PAF and AGEPC were inactivated by a 5-min incubation with ALF, the acid-labile factor in normal human serum that rapidly destroys AGEPC. 4. HS-PAF was demonstrated to be functionally similar to AGEPC by cross-desensitization experiments. In the absence of Ca++, HS-PAF and AGEPC cross-desensitized washed rabbit platelets to subsequent stimulation by either HS-PAF or AGEPC after recalcification. 5. HS-PAF was demonstrated to be structurally similar to AGEPC by several simple chemical tests for functional groups.
Specific reversal of cytolytic T cell-target cell functional binding is induced by free target cells.
Authors: Balk S P , Mescher M F
Published: December 2022

Reversal of specific cell-cell adhesions between allogeneic cytolytic T lymphocytes (CTL) and 51Cr-labeled target cells has been studied by using a functional assay for specific target cell binding. Functional adhesions between CTL and a tumor cell target, the P815 mastocytoma, were stable in suspension for greater than 5 hr. Addition of unlabeled target cells, however, resulted in rapid reversal of functional binding. This reversal appeared to be specific in that no reversal was induced by tumor cells of other H-2 types. Functional reversal of conjugates between CTL and labeled spleen cells syngeneic with P815 also occurred in the presence of unlabeled P815 cells or normal spleen cells of the appropriate H-2 type. The reversal by P815 was substantially more efficient than by normal spleen cells. Furthermore, normal spleen cells of the appropriate H-2 type did not induce reversal of CTL-P815 target conjugates. Purified plasma membranes from P815 cells did not specifically reverse functional binding of CTL to either P815 or normal spleen cell targets. These results demonstrate that functional CTL-target cell binding can be specifically reversed by interaction with free target cells. The rate of reversal appears to be dependent on the relative affinity of the CTL for the bound versus the free target cell. CTL may provide a useful system for studying reversal of specific cell-cell adhesions.
T cell recognition of Moloney sarcoma virus proteins. II. Phenotypes of the different lymphocyte subpopulations producing and responding to blastogenic factors and their relative frequencies during tumor regression.
Authors: Lee J C , Enjuanes L , Cicurel L , Ihle J N
Published: December 2022

The characteristics of the blastogenic response of splenic lymphocytes from MoLV/MSV immune mice was examined. Splenic lymphocytes from immune mice proliferate in vitro in response to the major virion envelope glycoprotein, gp70. Associated with this response is production of blastogenic factors that induce the proliferation of nylon wool-purified lymphocytes from either normal or immune mice. The phenotype of antigen-specific lymphocytes essential for the production of blastogenic factors was found to be Thy 1.2+, Lyt 1+, 2-. The induction of proliferation by blastogenic factors does not require the presence of antigen. Using splenic lymphocytes from either normal or immune mice, blastogenic factors predominantly induce the proliferation of a Thy 1.2-, Lyt 1-, 2- lymphocyte. As a consequence of responding to blastogenic factors, in vitro, approximately 50% of this lymphocyte population becomes Thy 1.2+, Lyt 1+ over a period of 3 days. The frequencies of lymphocytes producing and responding to blastogenic factors were found to show characteristic changes during the course of tumor growth and regression.
Actin content in lymphocytes: a proposed correlation with their recirculating properties.
Authors: Mely-Goubert B , Bellgrau D
Published: December 2022

The DNAase inhibition assay, which allows for the titration of monomeric and total actin content per cell, has been applied to various subpopulations of rat lymphocytes. We found that characteristic values are associated with functionally distinct subpopulations. Thus, thymus-dependent (T) lymphocytes have significantly higher monomeric and total actin per cell than bone marrow-derived (B) lymphocytes, irrespective of the separation procedure used (in vitro or in vivo). Moreover, these values appear to increase with the differentiation state of the cells within the T compartment (i.e., from thymus to lymph node to thoracic duct lymphocytes). The fact that the observed trends overlap the known in vivo recirculating abilities of the populations tested prompted us to discuss the possible involvement of intracellular actin in the control of the cell-surface deformability.
Regulation of T cell growth factor production: arrest of TCGF production after 18 hours in normal lectin-stimulated mouse spleen cell cultures.
Authors: Gullberg M , Ivars F , Coutinho A , Larsson E L
Published: December 2022

The detailed kinetics of TCGF accumulation in Con A-stimulated spleen cell cultures shows a maximum at 24 hr, with a subsequent decrease in activity. This decrease is not due to the appearance of inhibitory substances "masking" TCGF activity. Pulse experiments show that the rate of TCGF production falls sharply after 18 hr and is completely arrested after 24 hr of Con A stimulation. The arrest in TCGF production is the result neither of culture depletion in medium components nor of limiting accessory cell function or inactivation of the lectin, and it thus seem to be the result of inactivation of TCGF-producing T cells. This regulation is not the result of a TCGF-mediated feedback mechanism but rather of lectin-induced suppressive cells that appear in culture after 24 hr and turn off de novo production of TCGF in fresh cultures.
Activated T cells in the synovial fluid of arthritic patients. II. In vitro activation of the autologous blood lymphocytes.
Authors: Galili U , Rosenthal L , Klein E
Published: December 2022

Lymphocytes isolated from the synovial fluid of arthritic patients were shown to express characteristics of immunoactivated T cells, such as the formation of stable E rosettes and natural attachment to normal and malignant cells. During 5 days incubation in autologous serum, the synovial T cells reverted to resting state. If, however, the synovial serum was present in the culture, the activated state was maintained. The blood lymphocytes of these patients did not have the markers of activation. When blood lymphocytes were mixed in vitro with the autologous synovial T cells, a proportion of them acquired the capacity to form stable E rosettes and to express natural attachment. Synovial polymorphonuclear cells or synovial serum were without effect on the blood lymphocytes. This phenomenon may represent an in vivo mechanism for the perpetuation of the cellular immune reactivity in the joint cavity.
Immune responsiveness of HRS/J mice to syngeneic lymphoma cells.
Authors: Johnson D A , Meier H
Published: December 2022

HRS/J, hr/hr and hr/+ mice were evaluated for their ability to resist challenge with a syngeneic tumor, HTU, and for their ability to mount a protective immune response when immunized in vivo with inactivated HTU cells previous to challenge with viable tumors. The heterozygous (hr/+) mice responded more strongly than the homozygous (hr/hr) mice. This response was characterized by the presence of an enhanced ability of spleen cells from immunized mice to form blasts in vitro when incubated with purified murine leukemia viruses (MuLV). We conclude that the in vivo response of HRS/J mice against this tumor is directed, in part, against MuLV antigens expressed on the tumor cells and that the relatively weak response of hr/hr spleen cells to these antigens may be mechanistically linked to their tumor susceptibility.
Antigen-primed helper T cell function in CBA/N mice is radiosensitive.
Authors: Phillips N E , Campbell P A
Published: December 2022

CBA/N mice have an X-linked immunodeficiency that includes a deficient humoral response to sheep red blood cells (SRBC). In order to study the cellular mechanisms of this deficiency we have examined helper T cell function to SRBC in an adoptive transfer system by using 2 different sources of helper T cells. When thymocytes were used as the source of helper T cell precursors in an adoptive transfer system, CBA/N thymocytes were as effective as CBA/Ca thymocytes in inducing CBA/Ca bone marrow cells to develop into both direct and indirect anti-SRBC plaque-forming cells (PFC). However, when SRBC-primed, irradiated recipient mice were used as the source of helper T cells, primed and irradiated CBA/N recipients developed significantly fewer direct and indirect anti-SRBC PFC than similarly treated CBA/Ca recipients when reconstituted with CBA/Ca bone marrow cells and challenged with SRBC. This difference in radioresistant helper T cell function was also observed when primed, irradiated (CBA/N X DBA/2)F1 defective male and nondefective female mice were used as recipients of F1 female bone marrow cells and SRBC, confirming that this defect is a part of the X-linked CBA/N immunodeficiency. This deficiency in radioresistant helper T cell function in CBA/N mice does not appear to be due either to suppressor T cell function, or to a negative effect of the CBA/N environment on either B cell maturation, T cell-B cell cooperation, or helper T cell function. We conclude that antigen-primed helper T cell function in CBA/N mice is radiosensitive. Possible reasons for this are evaluated and discussed.
Effect of physical stress on sensitivity of lymphocytes to inhibition by prostaglandin E2.
Authors: Goodwin J S , Bromberg S , Staszak C , Kaszubowski P A , Messner R P , Neal J F
Published: December 2022

Physical stress is associated with depressed cellular immune function. We have found that lymphocytes from subjects undergoing either of 2 stressful events, cardiac surgery or childbirth, are more sensitive to inhibition by PGE2. For example, the concentration of PGE2 required for 50% inhibition of 3H-thymidine incorporation (ID50) into phytohemagglutinin-stimulated lymphocytes from patients undergoing cardiac surgery went from 1.5 X 10(-8) M on the day before surgery to 3 X 10(-9) M on the day after surgery. This increase in sensitivity to PGE2 was accompanied by a significantly decreased lymphocyte proliferative response (27 to 68% of control, depending on mitogen dose) and a 50% increase in the percentage of E rosette-positive cells with receptors for the Fc portion of IgG. The increased sensitivity to PGE and the depressed mitogen responses returned to preoperative values by day 10. The depressed mitogen responses of the postoperative patients were completely restored to normal by removal of glass-adherent cells before culture. In addition, the responses of the postoperative patients and the women in labor were partially restored by the addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures. Thus it would appear that physical stress causes lymphocytes to become more sensitive to prostaglandin E2, and the increased sensitivity to inhibition by this immunomodulator is responsible in part for the depressed cellular immune function after physical stress.
Cell-mediated lympholytic responses against autologous cells modified with haptenic sulfhydryl reagents. I. Effector cells can recognize two distinct classes of hapten-reactive self sites on cell surface proteins.
Authors: Levy R B , Shearer G M , Richardson J C , Henkart P A
Published: December 2022

Mouse spleen cells were modified with a sulfhydryl-reactive reagent, N-iodoacetyl-N'-(5-sulfonic-1-naphthyl) ethylene diamine (I-AED) and used as stimulator cells in primary in vitro cultures with unmodified spleen cells of the same strain. CTL could be readily demonstrated when tested on hapten-modified syngeneic target cells. These CML responses were hapten specific and H-2 restricted. In the H-2b strain, effector cell populations were identified that recognized AED in association with K-end and D-end coded self MHC products. Functional modification of the target cells by I-AED can be effectively blocked by prereacting the cells with other SH-reagents, which is consistent with CTL recognition of the hapten on cysteine residues. Since these premodifications of the cell surface do not block the functional modification by trinitrobenzene sulfonate (TNBS), the sulfhydryl-reactive compounds and TNBS modify distinct classes of cell surface groups as determined by CTL function. The results of antibody inhibition experiments are also consistent with this interpretation. Using fluorescent labeled anti-hapten antibodies, FACS II analysis showed that there are approximately 20-fold fewer AED than TNP groups on the approximately 20-fold fewer AED than TNP groups on the cell surface when equivalent concentrations of I-AED and TNBS are compared. The possibility is discussed that these sulfhydryl-reactive compounds can be used together with the H-2Kb mutants for the localization of H-2 coded self determinants recognized in association with foreign antigens.
Cell-mediated lympholysis responses against autologous cells modified with haptenic sulfhydryl reagents. II. Analysis of the genetic control and H-2-restricted pattern of cytotoxic responses to sulfhydryl and amino reactive reagents.
Authors: Levy R B , Henkart P A , Shearer G M
Published: December 2022

N-iodoacetyl-N'-(5-sulfonic-1-naphthyl)ethylene-diamine modified autologous cells are shown to induce respective high and low AED-self CTL responses by spleen cells from H-2b and H-2k mice. The lysis mediated by effector populations from both haplotypes was highly H-2 restricted. Cytotoxic responses induced by a 2nd sulfhydryl- (SH) specific reagent, dithionitrobenzoic acid (DTNB), were shown not to be cross-reactive at the effector cell level with AED-self but exhibited the same high and low CTL response patterns as those induced against AED-self. These Ir-effects reported for the 2 SH reactive compounds are discussed in relation to the opposite Ir-patterns demonstrated against a number of amino (NH2) reactive compounds. The difference of self-recognition sites is suggested to account for the contrasting results observed in the response patterns induced by SH- and NH2-reactive compounds. The AED-self CTL response was found to exhibit Kk-self over Db-self Ir regulation. Thus, this latter type of genetic control appears to function independently of whether the hapten is an SH- or NH2-reactive compound.
In vivo release of eosinophil chemoattractant activity in human allergic skin reactions.
Authors: Ting S , Zweiman B , Lavker R M , Dunsky E H
Published: December 2022

A search was made for in vivo release of factor(s) that may be responsible for prominent eosinophil accumulations in human allergic skin reactions. Using a specially designed skin chamber appended to the base of unroofed skin blisters, we have found at ragweed-challenged sites in sensitive subjects the release of significantly greater histamine (15 +/- 3 ng/ml) than at control sites (3 +/- 0.5 ng/ml). Eosinophil accumulation after 2 hr was also significantly greater on membrane filters appended to ragweed-challenged sites than control sites (55 +/- 15 vs 4 +/- 0.5). Intradermal injection of ultrafiltrates of the chamber fluids from antigen-challenged sites, but not of fluids from control sites, induced prominent eosinophil accumulation (mean = 25/mm2) when injected intradermally in autologous uninvolved skin. Neither ultrafiltered antigen solution nor histamine (employed in concentrations similar to those released in the chambers) evoked such in vivo responses when injected intradermally in the same subjects (mean = less than 1/mm2). The eosinophil responses to injected ultrafiltered chamber fluid from antigen-challenged sites peaked at 30 min, whereas even greater eosinophil responses to unaltered antigen started after 60 min. These findings suggest that in vivo release of a low m.w. factor or factors other than histamine is very likely responsible for at least part of the in vivo eosinophil accumulation in human allergic reaction sites. Additional findings suggest that a significant portion of the time lag between intradermal antigen and dermal eosinophil accumulation is encompassed by local mediator release.