bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural killer-sensitive targets stimulate production of TNF-alpha but not TNF-beta (lymphotoxin) by highly purified human peripheral blood large granular lymphocytes.
Authors: Peters P M , Ortaldo J R , Shalaby M R , Svedersky L P , Nedwin G E , Bringman T S , Hass P E , Aggarwal B B , Herberman R B , Goeddel D V 
Published: December 2022

Abstract
Highly purified populations of large granular lymphocytes (LGL) have been shown to mediate natural killer (NK) cell activity. The mechanism of target cell killing by NK cells is as yet undefined; however, it has been postulated that such killing may involve soluble cytotoxic factors produced and secreted by NK cells. The data presented show that NK-sensitive, but not NK-resistant, tumor cell lines induce highly purified populations of human LGL to produce factors with cytotoxic and/or cytostatic activities. We have identified one of these factors as tumor necrosis factor-alpha (TNF-alpha), and have shown that production of this factor is enhanced by recombinant human interferon-gamma (rHuIFN-gamma). We have also examined the role of TNF-alpha in the cytotoxic function of NK cells. The data show that although highly purified LGL populations produce low levels of TNF-alpha, the cytotoxic/cytostatic activity of this lymphokine on tumor target cells does not correlate with the cytotoxic activity of highly purified populations of LGL on tumor target cells. Furthermore, NK cell-mediated cytotoxicity is not reliably inhibited by antibodies directed against various epitopes of recombinant human TNF-alpha and/or recombinant TNF-beta (lymphotoxin) or rHuIFN-gamma. These data show that although TNF-alpha is produced by highly purified NK-containing LGL cell populations, this factor does not appear to be responsible for NK cell cytotoxicity against classical NK target cells such as Molt-4 or K562. We suggest that NK function can be attributed to a combination of factors rather than to a single factor alone, and that at least two major phenomena are involved in LGL function: the rapid cytotoxic events which lead to the cell lysis measured in classical in vitro NK assays such as against K562; and the release of factors such as TNF-alpha with cytotoxic/cytostatic activities which would inhibit the growth of invading tumor cells in vivo.
FcR epsilon+ lymphocytes and regulation of the IgE antibody system. V. Preliminary physicochemical characterization of the T cell-selective IgE-induced regulant EIRT.
Authors: Marcelletti J F , Katz D H 
Published: December 2022

Abstract
We previously showed that murine lymphoid cells exposed to elevated levels of IgE exhibit the de novo expression of Fc receptors for IgE (FcR epsilon), and the production of soluble mediators, which we have termed IgE-induced regulants (EIR). Described herein is the preliminary physicochemical characterization of one such regulant, that being the EIR responsible for the Lyt-2+ T cell-dependent expression of FcR epsilon and secretion of an IgE-binding factor (IgE-BF) which can potentiate IgE synthesis; the former activity has been denoted EIRT for its selectivity of action on T cells, and the latter activity has been termed enhancing effector molecule (EEM) for its presumed potentiating influence on IgE antibody synthesis. Characterized in parallel was the conventional lymphoid cell-derived cEIRT and a murine monoclonal T cell hybridoma-(MBI-2)-derived mcEIRT. EIRT from either source was shown to exhibit the characteristics of a protein with a molecular mass of 45 to 60 kd. Once enriched by gel filtration, neither cEIRT nor mcEIRT preparations displayed any other EIR-like activity except that of EIRT, as evidenced by the ability of these preparations to act selectively to induce the Lyt-2 T cell-dependent expression of FcR epsilon and the production of EEM, the lack of detectable SFA activity that could induce Lyt-1+ T cells to produce the IgE-BF denoted suppressive effector molecule (SEM), and the lack of detectable levels of the B cell-selective EIRB, as indicated by the incapacity of either preparation to induce B cell FcR epsilon expression. Neither cEIRT nor mcEIRT displayed IgE-binding affinity, in contrast to the EEM produced in response to stimulation with these regulants. The only EIR-like activity detected in the unfractionated supernatant fluid from cultures of the monoclonal T cell hybridoma MBI-2 was that of EIRT. Careful in vitro analysis established that such preparations did not contain enhancing factor of allergy (EFA), SFA, EIRB, or IgE-BF. Thus, the enhancement of IgE synthesis observed in animals given this mcEIRT preparation was most likely due to the activity of EIRT known to be present. During the course of these studies, clues as to the physicochemical nature of other EIR activities was obtained. Thus, upon molecular sieve analysis, two distinct molecular mass species of EIRB (one 15 to 20 kd and the other 30 to 35 kd) were demonstrated to be present in conventional lymphocyte-derived cEIR.(ABSTRACT TRUNCATED AT 400 WORDS)
Characterization of two distinct DR beta chain alleles at the beta III locus of the DR5 haplotype: beta III alleles are highly conserved.
Authors: Didier D K , Schiffenbauer J , Shuman S , Abruzzini L F , Gorski J , Watling D L , Tieber V L , Schwartz B D 
Published: December 2022

Abstract
The HLA-DR beta region of at least two members of the DRw52 (MT2) supertypic group (DR3, DR5, DRw6, and DRw8) has recently been shown to contain three beta-chain genes--beta I, beta II, and beta III, ordered in the direction of transcription. beta III is apparently a duplication of beta I. Both beta I and beta III are expressed, whereas beta II is a pseudogene. We previously reported the sequence of the DR5 beta I cDNA from the homozygous DR5 cell line Swei. We report here the sequence of two different DR5 beta III cDNA from the same cell line. The assignment of the genes of this and other members of the DRw52 supertypic group to specific loci allow comparisons between products of known alleles and between products of distinct loci. beta I allelic products showed approximately 11% divergence in the first domain, whereas beta I and beta III products showed 17% difference. These differences were clustered and found predominantly in the previously described variable regions (amino acid residues 9 through 13, 26 through 38, and 67 through 74). These data, coupled with the finding of shared variable regions among different DR beta chains, suggest gene conversion as a means of generating polymorphism in the beta I alleles. In contrast, the beta III allelic products showed less than 1% amino acid and nucleotide divergence in the first domain. These differences were outside the variable regions, and attributable to single nucleotide changes. The polymorphism at the beta I locus and the conservation at the beta III locus suggest selective pressure conserving the beta III locus and/or generating polymorphism at the beta I locus, and further suggest that gene conversion may be acting unidirectionally from beta III to beta I.
A synthetic analogue of Escherichia coli lipoprotein, tripalmitoyl pentapeptide, constitutes a potent immune adjuvant.
Authors: Lex A , Wiesmüller K H , Jung G , Bessler W G 
Published: December 2022

Abstract
Lipoprotein from the outer membrane of Escherichia coli and other Enterobacteriaceae constitutes a potent B lymphocyte mitogen and polyclonal activator in various species. Tripalmitoyl pentapeptide (S-(2,3-bis-(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-cysteinyl -(S)-seryl-(S)-seryl-(S)-asparaginyl-(S)-alanine) is a synthetic analogue of the N-terminal part of lipoprotein and has, in all assays tested, a biologic activity similar to native lipoprotein. It also exhibits a strong adjuvant activity in vitro: In the presence of 3.3 to 33.3 micrograms/ml of tripalmitoyl pentapeptide, the stimulation of the primary antibody response toward underivatized sheep red blood cells (SRBC) and toward trinitrophenylated (TNP-) SRBC was markedly enhanced, as measured by a direct hemolytic plaque assay. At optimal mitogen- and antigen-doses, plaque formation was increased up to 100-fold, and at suboptimal doses (0.03 to 0.3 microgram/ml) a 10- to 60-fold increase of plaque numbers was achieved. In the presence of tripalmitoyl pentapeptide, the antigen-specific IgM response was increased about sevenfold and the IgG response was augmented about 10-fold, as measured by ELISA. Similarly, in the secondary in vitro response to TNP-SRBC, a 7 to 10-fold enhancement of the antibody titer was obtained in the presence of the adjuvant. The application of tripalmitoyl pentapeptide and antigen had to occur concurrently in order to achieve a strong adjuvant effect. Addition of tripalmitoyl pentapeptide to the cell cultures 1 day after or 1 day before antigen application had no significant positive effect, and in several instances a decrease in antibody production was found. Thus, tripalmitoyl pentapeptide, a well-characterized synthetic product available in major amounts, constitutes a potent immune adjuvant for potential animal and clinical use.
Coexistence of a chemotactic factor and a retroviral P15E-related chemotaxis inhibitor in human tumor cell culture supernatants.
Authors: Wang J M , Cianciolo G J , Snyderman R , Mantovani A 
Published: December 2022

Abstract
Two sets of seemingly contradictory evidence have been reported concerning the effects of tumor cell products on the regulation of monocyte migration in vitro and presumably the extravasation of macrophages into tumors in vivo. The present study was designed to explore the relationship between chemotactic and anti-chemotactic products related to tumor cells: a tumor-derived chemotactic factor (TDCF) and retroviral P15E-related inhibitor(s) of chemotaxis. Culture supernatants of the human 8387 sarcoma and SW626 ovarian carcinoma were depleted of P15E-related antigens with immobilized anti-P15E monoclonal antibodies. This treatment produced a significant and consistent increase of the polarizing and chemotactic activity in the tumor cell supernatants. The material eluted from Sepharose-bound anti-P15E antibodies was devoid of chemotactic and polarizing activity and suppressed the polarization and migration of monocytes in response to chemoattractants. These results demonstrate the coexistence in culture supernatants of two human tumor cell lines of factors with opposite influences on monocyte chemotaxis. The data suggest that the entry of monocytes into neoplastic tissue may be regulated by the interplay of chemotactic and anti-chemotactic principals produced by tumor cells.
Characterization and activity of contrasuppressor T cells induced by type III pneumococcal polysaccharide.
Authors: Braley-Mullen H 
Published: December 2022

Abstract
Optimally immunogenic amounts of type III pneumococcal polysaccharide (S3) activate a population of contrasuppressor T cells (Tcs), which have been shown to play an important role in the induction of anti-S3 antibody responses. These Tcs belong to a unique T cell subset that has the surface phenotype Lyt 1+2- L3T4- I-J+ I-A+. These Tcs are also cyclophosphamide (Cy)-sensitive and sensitive to antilymphocyte serum (ALS) and mitomycin C. Tcs have antigen-binding receptors, indicating that any interactions of Tcs with B cells or T suppressor cells (Ts) (both of which also have antigen-binding receptors) must be via an antigen bridge rather than an idiotype-anti-idiotype interaction. Tcs are also Igh restricted in their action. Contrasuppression is manifest only when the Tcs are Igh compatible with both the Ts and the responding B cells. Tcs apparently mediate their effects by releasing a soluble factor, since a soluble factor extracted from Tcs is able to abrogate the effects of S3-specific Ts.
Morphology and lytic mechanisms of interleukin 3-dependent natural cytotoxic cells: tumor necrosis factor as a possible mediator.
Authors: Jadus M R , Schmunk G , Djeu J Y , Parkman R 
Published: December 2022

Abstract
Populations of interleukin 3 (IL 3)-dependent cells can be derived from mouse bone marrow that display natural cytotoxicity (NC) against Wehi-164 target cells but do not display natural killing against YAC-1 cells. These bone marrow-derived NC cells cultured up to 2 mo in IL 3 do not contain rearranged T cell receptor beta-chain genes. They appear to be mast-like cells by electron microscopy and contain heterogeneous type granules. The molecules that mediate NC appear to be contained in these granules and are preformed because protein synthesis inhibitors have no effect on the capacity of IL 3-dependent NC cells to lyse Wehi-164 target cells. In addition to the IL 3-dependent bone marrow-derived cells, the basophilic leukemia cells, RBL-1, but not P815 mastocytoma cells were found to mediate NC against Wehi-164 cells. Both bone marrow-derived NC and RBL-1 cells can lyse L929 cells in 18 hr, suggesting that the putative NC mediator may be related to lymphotoxin/tumor necrosis factor (TNF). Recombinant human TNF displayed identical properties as NC cells; both entities possessed the same target cell specificity and had similar kinetics of target cell killing. The use of polyclonal rabbit antimouse TNF antibody blocked the actions of NC cells. Thus we believe that the mediation of NC is through the actions of a TNF-like molecule.
Suppressor T lymphocytes from lepromatous leprosy skin lesions.
Authors: Modlin R L , Mehra V , Wong L , Fujimiya Y , Chang W C , Horwitz D A , Bloom B R , Rea T H , Pattengale P K 
Published: December 2022

Abstract
The immune response in leprosy forms a spectrum with lepromatous leprosy patients exhibiting specific unresponsiveness to antigens of Mycobacterium leprae. This unresponsiveness is thought to be related to the prevalence of T8-positive lymphocyte in these lepromatous lesions. To analyze the immunoregulatory function of these T8 cells, we developed simple procedures to extract lymphocytes from skin biopsy specimens of patients with leprosy. These lymphocytes were sorted for T8 and T4 positive cells, and cell lines were established by expansion with interleukin 2 (IL 2) and irradiated feeder cells. All T8 positive lines tested were positive for IL 2 receptors and HLA-DR determinants. These lines were additionally assayed for lepromin-induced suppression of the normal peripheral blood lymphocyte Con A proliferative response. Thirteen of 32 lines from six lepromatous patients showed significant suppressor activity, whereas nine lines from six tuberculoid patients and one line from normal peripheral blood failed to show suppression (p less than 0.001). Taken together, the finding of M. leprae-triggered suppressor cells within lepromatous skin lesions may in part explain the M. leprae unresponsiveness of lepromatous leprosy patients.
Experimental allergic encephalomyelitis mediated by murine encephalitogenic T cell lines specific for myelin proteolipid apoprotein.
Authors: Satoh J , Sakai K , Endoh M , Koike F , Kunishita T , Namikawa T , Yamamura T , Tabira T 
Published: December 2022

Abstract
T cell lines specific for bovine myelin proteolipid apoprotein (PLP) were established from SJL/J mice. The line cells bore surface phenotypes of T helper/inducer cells (Lyt-1+, Lyt-2-, L3T4+) and responded well to bovine, rat, and guinea pig PLP but not to myelin basic protein. One line responded to major PLP, and another responded to both major PLP and DM-20, which are the two major intrinsic membrane proteins of the central nervous system (CNS) myelin. Intraperitoneal inoculation of 4 to 30 X 10(6) PLP-activated line cells followed by injection of pertussis vaccine induced acute inflammatory disease of the CNS, with typical clinical signs of EAE mostly in a week in recipient mice that had been treated with low-dose irradiation. Almost all animals recovered completely, and two of the 12 animals relapsed 42 or 75 days after inoculation. The lesions were restricted to the CNS and were characterized by perivascular and parenchymal infiltration of inflammatory cells, fibrin deposit, and demyelination. In the severe lesions, axons were also damaged. These observations suggest that PLP is a definite encephalitogen, and PLP-sensitized effector T cells induce inflammatory demyelination in the CNS.
Quantitation of T cell antigen-binding molecules (TABM) in the sera of nonimmunized, immunized, and desensitized mice.
Authors: Cone R E , Gerardi D A , Davidoff J , Petty J , Kobayashi K , Cohen S 
Published: December 2022

Abstract
Heterologous antibodies to non-MHC-restricted T cell antigen-binding molecules (TABM) were used in an ELISA to detect and quantitate TABM levels in the sera of nonimmune mice and in mice immunized and/or desensitized to methylated bovine serum albumin (MBSA). TABM were detected at low levels in sera from nonimmune and immune mice. Amounts of TABM rose 300-fold in MBSA-immune mice within 12 hr of a desensitizing injection of MBSA, and rapidly returned to pre-desensitization levels. Serum TABM were purified by precipitation with 50% (NH4)2SO4 and chromatography in carboxymethylcellulose. The purified TABM were Mr 30,000 to 37,000 reduced, 72,000 nonreduced, and had a pI range of 5.5 to 7.1. A portion of the elevated TABM in desensitized mice bound MBSA specifically, whereas TABM from the sera of nonimmune/nondesensitized mice did not bind MBSA. The timing of the appearance of TABM early in desensitization suggests the possibility that they may play a role in the subsequent appearance of suppressor cells in later stages of this phenomenon. In addition, the results presented here raise the possibility that fluctuations in TABM levels might prove to be a sensitive indicator of immunoregulatory status in general.
A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32.
Authors: Weis J H , Morton C C , Bruns G A , Weis J J , Klickstein L B , Wong W W , Fearon D T 
Published: December 2022

Abstract
The alternative or classical pathways for complement system component C3 may be triggered by microorganisms and antigen-antibody complexes. In particular, an activated fragment of C3, C3b, covalently attaches to microorganisms or antigen-antibody complexes, which in turn bind to the C3b receptor, also known as complement receptor 1. The genes encoding the proteins that constitute the C3-activating enzymes have been cloned and mapped to a "complement activation" locus in the major histocompatibility complex, and we demonstrate in this study such a locus on the long arm of chromosome 1 at band 1q32.
The immunostimulatory effect of T cells and T cell lymphokines on murine fetally derived placental cells.
Authors: Athanassakis I , Bleackley R C , Paetkau V , Guilbert L , Barr P J , Wegmann T G 
Published: December 2022

Abstract
Evidence for maternal immune recognition of the fetus can be found during pregnancy, yet the conceptus remains unharmed. Indeed, in some cases immunizing the mother with cells sharing histocompatibility antigens with the fetus is beneficial to fetal survival. This could be due to the effect of maternally derived lymphokines on placental growth and function, according to the immunostimulation hypothesis. We demonstrate here that placental cells in culture proliferate upon the addition of T cell-derived lymphokines. The lymphokine activity has been separated from IL 2 and B cell growth factor, and copurified with IL 3 and granulocyte-macrophage colony-stimulating factor (CSF-GM). Recombinant CSF-GM and recombinant IL 3 showed a similar effect. The placental cells that proliferate in culture are of fetal origin and are characterized by strong adherence, phagocytosis, nonspecific esterase staining, and response to the macrophage-specific colony-stimulating factor CSF-1. In addition, treatment of pregnant females with anti-thymocyte serum as well as anti-Ly-2.1 monoclonal antibody, at gestational times before Ly-2 antigen appearance in the fetus, leads to a reduction of the proliferative and phagocytic capacity of day 12 placentae. These results clearly demonstrate that maternal T cells act upon fetally derived placental cells to improve their proliferative and phagocytic potential, and thus provide evidence for the immunostimulatory role of these cells during pregnancy.
Recognition of the beta-2 microglobulin-B molecule by a CTL clone.
Authors: Kurtz M E , Martin-Morgan D , Graff R J 
Published: December 2022

Abstract
In this report we offer evidence that the beta-2 microglobulin-B (beta 2M-B) molecule is recognized by a cytotoxic T lymphocyte (CTL). Production of GA5, a CTL clone reactive against a membrane antigen with the same strain distribution pattern as beta 2M-B, is described. This clone lysed syngeneic target cells in which native beta 2M-A molecules had been exchanged with beta 2M-B molecules by incubating the cells in serum from beta 2M-B-positive mouse strains. Conversely, the CTL clone GA5 failed to lyse its specific target when beta 2M-B molecules had been exchanged with beta 2M-A molecules by incubating the cells in serum from beta 2M-A-positive, beta 2M-B-negative mouse strains. Strain combinations were chosen so as to limit reactivity to beta 2M and to preclude reactivity to H-3 antigens, thus indicating CTL clone GA5 to be reacting specifically with beta 2M-B.
Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation.
Authors: Budd R C , Cerottini J C , Horvath C , Bron C , Pedrazzini T , Howe R C , MacDonald H R 
Published: December 2022

Abstract
The Pgp-1 glycoprotein was identified on a minor (27%) subset of peripheral Lyt-2+ or L3T4+ T cells. In contrast, mature medullary-type thymocytes (Lyt-2+ L3T4-, Lyt-2- L3T4+) were nearly devoid of cells expressing detectable surface Pgp-1. The appearance of peripheral Pgp-1- T cells was found to be thymus dependent, as demonstrated by the diminished proportion of Pgp-1- T cells after thymectomy and their virtual absence in athymic nude mice. The subsequent acquisition of surface Pgp-1 was found to be a stable differentiation event occurring concomitantly with primary antigenic stimulation; selected Pgp-1- mature T cells from thymus or periphery acquired constitutive expression of Pgp-1 after stimulation in vitro with alloantigen or mitogens. These observations were extended by studies in vivo showing that immunization with various antigens augmented the percentage of Pgp-1+ spleen cells within the Lyt-2+ subset. Furthermore, the frequencies of antigen-specific CTLp, after immunization by any of three different antigens tested, were greatly enriched in the Pgp-1+ compared with the Pgp-1- subpopulations. Peritoneal exudate Lyt-2+ cells, after a localized allograft rejection, demonstrated a particularly prominent Pgp-1+ subpopulation (78%) that contained virtually all the allospecific cytolytic activity. A model consistent with all of these data proposes that mature thymocytes lacking surface Pgp-1 upon emigration to the periphery acquire its expression at the time of primary antigenic stimulation. Hence, expression of Pgp-1 among peripheral T cells is an important differentiation marker for identifying antigen-stimulated memory T cells.