bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2.
Authors: Farrar W L , Johnson H M , Farrar J J 
Published: December 2022

Abstract
The activation of alloantigen-specific cytotoxic T lymphocyte precursors is dependent upon the presence of both macrophages and helper T cells or regulatory molecules derived from these facilitative cells. Three biochemically distinct helper factors have been identified: interleukin 1 (macrophage-derived), Interleukin 2 (T cell derived), and immune interferon. All 3 factors are found in supernatants of mixed lymphocyte cultures (MLC), however, the removal of macrophages from these cultures completely ablates the production of these factors as well as the induction of cytotoxic T lymphocytes (CTL). The addition of IL 2 to these macrophage-depleted MLC restores the ability of responder T cells to: 1) bypass the requirement for macrophage soluble function, 2) produce immune interferon, and 3) generate CTL. The kinetics and dose response of immune interferon production in response to IL 2 correlates with the generation of CTL. The production of immune interferon as well as the generation of CTL requires T cells, alloantigen, and IL2. Furthermore, the induction of CTL by IL2 was neutralized by the addition of anti-immune interferon. These data suggest that: 1) the regulation of immune interferon production is based on a T to T cell interaction mediated by IL 2, and 2) immune interferon production may be required for IL 2 induction of CTL. These findings are consistent with the hypothesis that the induction of CTL involves a linear cell-factor interaction in which IL 1 (macrophage-derived) stimulates T cells to produce IL 2, which in turn stimulates other T cells to produce immune interferon and become cytotoxic.
Plasminogen activation by normal B lymphocytes, a function associated with the cell membrane.
Authors: Maillard J L , Favreau C 
Published: December 2022

Abstract
When purified murine plasminogen was added to cultures of mouse spleen B cells, active plasmin progressively appeared in the supernatants. This reaction, resulting from the specific cleavage of the plasminogen by lymphocyte plasminogen activator (LPA), was measured in a fibrinolysis assay using 125I-fibrinogen. T cells were totally ineffective; under certain conditions, they could even antagonize the B cell action. Of the various B populations studied, i.e., obtained from spleen, lymph nodes, or blood of various mouse strains, all expressed the same property of plasminogen activation, which concerned mainly medium-sized B cells. Since only slight activities were detected in extracellular or intracellular compartments, a membrane-associated proteolytic enzyme may be responsible for plasminogen activation. Submitted to a series of group-specific antiproteases, the lymphocyte plasminogen activator essentially behaved as a serine-protease, with sensitivity to diisopropyl fluorophosphate, phenyl methyl sulfonyl fluoride, and nitro phenyl guanidino benzoate. The fast renewal of the enzyme in the membrane was also demonstrated by different techniques, using modifiers of cell physiology, like cycloheximide and dexamethasone, or following the reexpression of the enzyme by the cell kinetically.
Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. I. Characterization of a soluble suppressor T cell proliferation.
Authors: Greene W C , Fleisher T A , Waldmann T A 
Published: December 2022

Abstract
When activated with the mitogenic lectin, concanavalin A, a subset of human peripheral blood mononuclear cells differentiate into potent suppressor cells that negatively modulate both cellular and humoral immune reactions. In addition to inhibitory cell-cell interactions, these regulatory cells elaborate a soluble immune suppressor supernatant (SISS) containing at lest 2 distinct suppressor factors. One of these factors, SISS-T, inhibits mitogen- and antigen-stimulated T cell proliferation, whereas the other, SISS-B, inhibits B cell immunoglobulin production. Characteristics of the latter inhibitor are reported in the companion paper. Properties of the soluble suppressor of T cell proliferation (SISS-T) include: 1) a m.w. of 30 to 45,000, 2) inhibition by a noncytotoxic mechanism, 3) instability at 56 degrees C, 4) loss of activity in the presence of the monosaccharide N-acetyl-D-glucosamine and retention on N-acetyl-D-glucosamine affinity columns, 5) binding to the same surface glycoprotein receptors recognized by the lectins wheat germ agglutinin and Agaricus bisporus lectin, which produce similar inhibition of mitogen- or antigen-induced lymphocyte proliferation, 6) elaboration by cells irradiated with 500 and 2000 R but not 6000 R, 7) a minimum requirement for 24 hr of lectin stimulation for production, and 8) elaboration by adherent cells or alternatively cellular collaboration requiring the participation of adherent cells. These data indicate that human suppressor cells are capable of modulating T cell function via the production of a soluble saccharide-specific factor(s) that interacts with defined surface glycoprotein or glycolipid receptors. These same receptors recognized by the suppressive endogenous lectin are also activated by selected exogenous nonmitogenic lectins that produce similar inhibition of T cell metabolism.
Allergic neuritis: a neuritogenic peptide from the P2 protein that induces disease in rats.
Authors: Szymanska I , Ishaque A , Ramwani J , Eylar E H 
Published: December 2022

Abstract
Peptide CN1, a large 93 residue peptide, derived from residues 21-113 of the bovine and rabbit P2 protein of sciatic nerve myelin, induces severe allergic neuritis in Lewis rats. When complexed with phosphatidylserine and tested at 50 microgram dosage in Freund's complete adjuvant, it induces severe clinical and histologic signs (cellular infiltration and demyelination of the sciatic nerve) in most animals. It is as potent in disease induction as the P2 protein on a weight basis. In contrast, when not complexed with phosphatidylserine, Peptide CN1 induced only mild clinical signs and histologic lesions in 3 of 10 rats. CNBr peptides CN2 and CN3, derived from the carboxyl and amino terminal ends, respectively, were not active. Spleen and lymph node cells from rats sensitized to Peptide CN1 responded to both P2 and Peptide CN1 in culture in the mitogenic assay. These data show that the major neuritogenic domain for the rat resides in the CN1 region.
Spontaneous cytotoxicity against virus-infected cells: relationship to NK against uninfected cell lines and to ADCC.
Authors: Weston P A , Jensen P J , Levy N L , Koren H S 
Published: December 2022

Abstract
Cellular immunoadsorption and cold cell competition assays were used to examine the specificity of NK. Lymphocytes nonadherent to monolayers of cells persistently infected with Sendai virus (SV-HEp2) were almost totally depleted of NK against the uninfected tumor cell lines K562, MOLT-4, and HSB, as well as against SV-HEp2, when assayed immediately after separation. Lymphocytes adherent to SV-HEp2 monolayers were also partially depleted of NK against these targets. After overnight incubation, the nonadherent cells remained relatively depleted of NK against all targets, compared to controls. The adherent cells displayed a variable amount of activity, depending on the donor; in all cases, however, substantial NK activity was observed in this fraction against all targets, infected and uninfected. Exogenous interferon failed to augment the activity of the nonadherent lymphocyte fraction. Cellular immunoadsorption on monolayers of K562 or HSB was similarly found to partially deplete NK against SV-HEp2, as well as against the homologous cells. Cold cell inhibition studies showed that SV-HEp2 and, to a lesser extent, HEp2, could inhibit the lysis of K562; similarly, K562 could partially inhibit the lysis of SV-HEp2. We concluded that infected and uninfected target cells are lysed by overlapping populations of NK effector cells. In addition, the ADCC activity of SV-HEp2-adherent and nonadherent lymphocyte fractions was examined immediately after separation. Whereas the nonadherent lymphocytes were depleted of both ADCC and NK, the adherent lymphocytes were partially depleted of NK yet contained high levels of ADCC activity.
Delayed, relapsing experimental allergic encephalomyelitis in mice.
Authors: Lublin F D , Maurer P H , Berry R G , Tippett D 
Published: December 2022

Abstract
Immunization of female SJL mice with an emulsion of lyophilized mouse spinal cord, pertussis vaccine, and complete Freund's adjuvant produces a delayed and often relapsing form of experimental allergic encephalomyelitis (DR-EAE). The mice develop initial signs of disease an average of 6 mo after immunization. Relapses occurred 2 wk to 11 mo after the initial illness. Some animals had multiple relapses. Pathologic examination of the brain and spinal cord revealed perivascular infiltration of mononuclear cells with acute demyelination. Areas of subacute and chronic demyelination ("plaques") were also seen. This model produces a clinical course of relapsing-remitting disease with pathologic evidence of both recent and old inflammatory lesions at various levels of the central nervous system. It thus more closely resembles multiple sclerosis than acute EAE.
The transformation of adult but not newborn human lymphocytes by Epstein Barr virus and phytohemagglutinin is inhibited by interferon: the early suppression by T cells of Epstein Barr infection is mediated by interferon.
Authors: Thorley-Lawson D A 
Published: December 2022

Abstract
In a previous study, it was demonstrated that T cells from adult individuals were able to suppress the transformation of B cells after infection by EBV. In this paper, it is shown that this suppression is mediated by interferon. Thus, the suppression is abrogated by anti-interferon serum and mimicked by human leukocyte interferon. Furthermore, the interferon is released in response to the virus-infected B cell, not the virus alone. The relevance of these results to previous clinical evidence, indicating a role for interferon in recovery from EBV infection, is discussed. Interferon will also suppress the transformation of adult B lymphocytes by the mitogen phytohemagglutinin (PHA). However, interferon at concentrations 2 to 3 orders of magnitude higher was unable to suppress the transformation of neonatal B lymphocytes by either EBV or PHA. These experiments suggest that EBV and PHA induced transformation share a common interferon sensitive step. Lastly, the resistance of newborn lymphocytes to the protective effect of interferon may be an important consideration in the application of interferon as an antiviral or anti-tumor agent.
Cytolytic T lymphocyte precursor cells in congenitally athymic C57BL/6 nu/nu mice: quantitation, enrichment, and specificity.
Authors: Maryanski J L , MacDonald H R , Sordat B , Cerottini J C 
Published: December 2022

Abstract
A sensitive limiting dilution microculture system was used to obtain minimal estimates of the frequency of CTL precursor cells (CTL-P) in spleens from 5- to 14-mo-old C57BL/6 nu/nu mice. Frequency determinations of CTL-P directed against H-2d alloantigens ranged from 1/159,000 to 1/12,400. The relatively low frequency of CTL-P was enriched nearly 10-fold (to 1/2300) by passage of nude spleen cells over a column of nylon wool. After priming nude spleen cells for 7 days in conventional MLC, 1 to 3% of the MLC cells could be operationally identified as CTL-P. Furthermore, the progeny of MLC-primed nude CTL-P were specifically cytolytic for target cells of the strain used for priming. Such a system may be useful for analyzing the specificity repertoires of cells of the T cell lineage that have not undergone thymic influence.
Frequency analysis of immunoglobulin V-gene expression and functional reactivities in bone marrow B cells.
Authors: Benner R , Rijnbeek A M , Schreier M H , Coutinho A 
Published: December 2022

Abstract
Frequency of immunocompetent B cells in bone marrow has been determined in vitro under culture conditions that allow the development in vitro under culture conditions that allow the development of every growth-inducible B cell into a clone of IgM-secreting PFC. Three limiting dilution culture systems were employed: a specific helper assay with SRBC as antigen and using activated T helper cells, a nonspecific helper assay using Con A-induced factors as a source of help, and polyclonal activation with LPS. From unseparated, normal C57BL/6J bone marrow 1 in 2200 to 1 in 2820 B cells were induced to form a clone of PFC to SRBC in each of the 3 systems. This corresponds to a frequency of 1 SRBC-specific clone in every 900 IgM-secreting LPS-reactive clones. The frequencies of specific plaque-forming B cell clones in terms of LPS-reactive B cells was 1 in 36 for NNP1-SRBC, 1 in 58 for TNP30-SRBC, 1 in 75 for NIP1-SRBC, and 1 in 230 for TNP3-SRBC. These frequencies of v-gene expression in bone marrow B cells are of the same magnitude as the corresponding frequencies for splenic B cells. Bone marrow B cells are also fully susceptible to stimulation by antigen in combination with either specific or nonspecific T cell help, as well as polyclonal activation by LPS, since every 3rd Ig-positive cells in marrow could be induced to form a clone of IgM-secreting cells. There is thus no difference in immunocompetence between surface Ig-bearing B cells from bone marrow and spleen.
Requirement of a combination of a saturated and an unsaturated free fatty acid and a fatty acid carrier protein for in vitro growth of lymphocytes.
Authors: Spieker-Polet H , Polet H 
Published: December 2022

Abstract
Two FFA, 1 saturated and 1 unsaturated, and a FFA carrier protein are essential for in vitro growth of Con A-stimulated lymphocytes. Optimal growth was obtained with a combination of palmitic and oleic acid. As carrier proteins, serum albumin and beta-lactoglobulin served equally well. Palmitic and oleic acid could be replaced by other saturated and unsaturated FFA, respectively. The effectiveness of unsaturated FFA was influenced by the chain length, the number of double bonds, and the configuration at the double bond. The position of the double bond appeared to have no effect. 125I-HSA binds to lymphocytes in a specific and nonspecific way. beta-Iac competes with 125I-HSA for the SA-binding sites. The specific binding and the growth supporting ability of SA have a similar dose response.
Synergism between two helper cell subpopulations characterized by different radiosensitivity and nylon adherence.
Authors: Agarossi G , Mancini C , Doria G 
Published: December 2022

Abstract
The present work extends our previous results on the radiosensitivity of the helper cell function. Two helper cell subpopulations, 1 radiosensitive and the other radioresistant, have been demonstrated in the spleen of mice at different times after priming with HRBC. The radiosensitive subpopulation increases with the increasing time interval between carrier-priming and irradiation. The 2 cell subpopulations have been further characterized by different nylon adherence properties: radioresistant helper cells adhere to nylon wool, whereas radiosensitive cells pass through. The 2 cell subpopulations were separated by x-irradiation and nylon wool filtration, and their helper activity was assessed separately or after recombination. The results favor the notion that 2 functionally independent helper T cells, as characterized by different radiosensitivity and nylon adherence, participate synergistically in the helper activity of primed spleen cells.
Functionally distinct helper T cells enriched under different culture conditions cooperate with different B cells.
Authors: Imperiale M J , Faherty D A , Sproviero J F , Zauderer M 
Published: December 2022

Abstract
Helper T cells selected from KLH-primed lymph node cells under different in vitro conditions were analyzed for the ability to cooperate in secondary hapten-specific antibody responses. It is shown that carrier-specific, MHC-restricted helper T cells selected in low-density cultures cooperate with equal efficiency in either PC-specific or DNP-specific responses. In the presence of both PC-specific and DNP-specific B precursors, however, such T cells are limited to participate in only one helper event in vitro. In contrast, the predominant helper T cell in a second population maintained in high-density lymph node cultures cooperates, presumably through a soluble factor, with multiple B precursors. These properties correspond to those previously described for specific and nonspecific effector functions. The experiments reported here further demonstrate that different B cells respond in vitro to carrier-specific and nonspecific helper signals.
The effect of T cell growth factor on the cell cycle of primate T cells.
Authors: Brown R L , Griffith R L , Neubauer R H , Rabin H 
Published: December 2022

Abstract
The effect of T cell growth factor (TCGF) on the cell cycle of four T cell lines that differed in their response to TCGF was studied. Activated normal marmoset T cells (OH-1) were totally dependent on the addition of TCGF for long-term proliferation. In the absence of TCGF, the cells were incapable of traversing the cell cycle and became arrested in G1. The addition of TCGF to arrested OH-1 cells stimulated them to enter the S phase after a lag phase of 24 to 33 hr. The TCGF-stimulated cells reached a maximum of cells in the S phase by 12 hr after the initiation of DNA synthesis. TCGF was required for a minimum of 18 hr before cells would enter the S phase. In the absence of TCGF, activated owl monkey (8I) and human (RG) lymphocytes displayed a TCGF-sensitive block; addition of TCGF stimulated these cells to enter the S phase after 12 and 16 hr, respectively. In contrast, an owl monkey tumor-derived T cell line (OMT-1), not dependent on exogenous TCGF for proliferation, was able to progress slowly through the cell cycle without a TCGF-sensitive block. These cells responded to TCGF by showing an initial increase in cells that entered the S phase after a lag of 6 hr and a continuing movement of additional cells into S over the course of the next several hours.
Regulation of macrophage suppression and cytotoxicity by interferon role of Ia-bearing macrophages.
Authors: Boraschi D , Niederhuber J E 
Published: December 2022

Abstract
Resident peritoneal M phi of C3H/HeN mice co-cultured with splenic lymphocytes suppressed proliferation to mitogens. This M phi-mediated suppression was significantly reduced by in vitro treatment of M phi with fibroblast interferon (IFN-beta). Conversely, M phi-mediated natural tumor cytolysis was augmented by M phi treatment with IFN-beta. Depletion of Ia-bearing (Ia+) M phi by means of anti-Ia serum and C treatment did not affect M phi-mediated suppression or M phi-mediated natural cytotoxicity. This suggested that Ia-negative (Ia-) M phi were responsible for the effector phase of these two M phi functions. The IFN-beta-induced increase in M phi cytolysis was not affected by depletion of Ia+ cells; however, modulation of suppressive activity by IFN-beta was found to be highly dependent on the presence of Ia+ M phi. This observation indicated that different M phi subpopulations were involved in the regulation of suppressive and tumoricidal activity. The results indicating different regulatory M phi were supported by experiments with C3H/HeJ mice. C3H/HeJ M phi do not develop high cytolytic activity in response to a variety of stimuli; however, M phi from C3H/HeJ mice were able to exert suppressive activity, which was reduced by treatment with IFN-beta.
Chemically related antigens compete for presentation by accessory cells to T cells.
Authors: Werdelin O 
Published: December 2022

Abstract
Immune responsiveness of guinea pigs to dinitrophenyl-poly-L-lysine (DNP-PLL) and to the lysine-rich random copolymer of L-glutamic acid and L-lysine (GL) are both controlled by the "poly-L-lysine gene." We demonstrate that accessory cells of responder strains can be made incapable of presenting DNP-PLL to response T cells in assays for proliferation by in vitro exposure of the cells to GL before and during their exposure to DNP-PLL. The inhibition was not rapidly reversible, because GL preexposed accessory cells that were cultured for 2 hr in GL-free medium were still refractory to pulsing with DNP-PLL. In contrast, DNP-PLL had only a moderate inhibitory effect on accessory cell presentation of GL. Unconjugated poly- and oligo-lysines also inhibited the ability of accessory cells to present DNP-PLL, but inhibitory activity was displayed only by homopolymers containing eight to 12 or more residues in the chain. The homopolymers of D-lysine, L-arginine, and L-glutamic acid, and lysine-free glutamic acid-rich copolymers had little or no inhibitory effect. The results are interpreted to mean that antigens to which responsiveness is regulated by the same Ir gene compete for presentation by accessory cells. This may reflect a competition for the Ir gene product of the antigen-presenting cell.
Spleen cells from adult mice given total lymphoid irradiation (TLI) or from newborn mice have similar regulatory effects in the mixed leukocyte reaction (MLR). II. Generation of antigen-specific suppressor cells in the MLR after the addition of spleen cells from newborn mice.
Authors: Okada S , Strober S 
Published: December 2022

Abstract
Spleen cells from newborn BALB/c mice were added to the mixed leukocyte reaction (MLR) between a variety of responder and stimulator cells. The newborn cells nonspecifically suppressed the uptake of (3H)-thymidine and the generation of cytolytic cells regardless of the responder-stimulator combination used. Suppressor cell activity fell rapidly during the first 4 days after birth, and could not be detected by day 20. Newborn spleen cells inhibited the generation of nonspecific suppressor cells during the MLR but did not inhibit the generation of antigen-specific suppressor cells. Thus, newborn spleen cells exhibit a pattern of regulation of the MLR similar to that reported previously for spleen cells from adult mice given total lymphoid irradiation (TLI). These regulatory interactions provide a model that explains the ease of induction of transplantation tolerance in vivo in newborn mice and in TLI-treated adult mice.
Production of human suppressor T cell hybridomas.
Authors: Greene W C , Fleisher T A , Nelson D L , Waldmann T A 
Published: December 2022

Abstract
To study human T cell suppression of immunoglobulin (Ig) synthesis with homogeneous populations of immunoregulatory cells, human suppressor T cell hybridomas were prepared by somatic cell fusion of concanavalin A-activated peripheral blood T cells with hypoxanthine-guanine phosphoribosyltransferase-(HGPRT, EC 2.4.2.8) deficient human leukemic CEM T cells. After selection in hypoxanthine-aminopterin-thymidine (HAT) medium and cloning by limiting cell dilution, two human T cell hybridomas were identified that produced 60 to 80% suppression of in vitro polyclonal immunoglobulin production when cocultured with pokeweed mitogen- (PWM) stimulated peripheral blood lymphocytes. Further, one of the suppressor T cell hybridomas constitutively secreted a soluble suppressor factor(s) (TsF) of m.w. 70,000 to 85,000 daltons, which produced reversible noncytotoxic inhibition of lectin-activated B cell Ig production. In contrast, this TsF did not inhibit lectin- or antigen-induced T cell proliferation, nor did it interfere with the generation or effector function of cytotoxic T cells. Additional studies indicated that this Tsf acts directly on B cells or monocytes rather than indirectly modulating the activity of immunoregulatory T cells. In summary, these studies suggest that techniques of somatic cell fusion may provide a valuable approach to further study human immunoregulatory cell-cell interactions as well as provide a source of sufficient quantities of important lymphokines for further purification and characterization.