bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refractoriness to Migration Inhibitory Factor of Macrophages of LPS Nonresponder Mouse Strains
Authors: Tagliabue Aldo , McCoy James L. , Herberman Ronald B. 
Published: December 2022

Abstract
The responsiveness to macrophage migration inhibitory factor (MIF) of peritoneal exudate cells (PEC) from the LPS unresponsive C3H/HeJ and C57BL/10ScCR mice was assessed by the indirect agarose microdroplet macrophage migration inhibition assay. No migration inhibition with PEC from C3H/HeJ nor C57BL/10ScCR mice was detected, whereas PEC from both C3H/HeN and C57BL/10Sn mice were significantly inhibited by even a 1/32 dilution of MIF-containing supernatants. Responsiveness to MIF of C3H/HeJ PEC could, however, be induced. In vivo inoculations of Mycobacterium bovis, strain BCG, 7 days before in vitro assay rendered C3H/HeJ PEC responsive to MIF. The lack of responsiveness to MIF by C3H/HeJ PEC appeared related to some form of suppression, since a mixture of PEC from C3H/HeN mice with 10 to 15% PEC from C3H/HeJ mice resulted in undetectable migration inhibition at any MIF dilution. In contrast to the usual lack of responsiveness of their macrophage to MIF, C3H/HeJ mice were able to produce MIF in response to PPD as well as their counterpart C3H/HeN mice after BCG sensitization. These results demonstrate that macrophages from C3H/HeJ and C57BL/10ScCR mice are unable to be inhibited in their in vitro migration of MIF (possibly being directly or indirectly influenced by a suppressor cell), whereas lymphoid cells from at least one of these strains, the C3H/HeJ mice, can produce MIF in response to antigenic stimulation.
Nonimmunologic Complement Activation in Normal Human Serum Induced by Radiographic Contrast Media
Authors: Kolb William P. , Lang Joseph H. , Lasser Elliott C. 
Published: December 2022

Abstract
Two different radiographic contrast media (RCM), iothalamate and iodipamide, induced the activation of several complement (C) components in normal, genetically C2-deficient and agammaglobulinemic human sera in vitro. This activation was dose dependent and demonstrable by a reduction in whole C as well as C4, C2, C3, and C5 hemolytic activities. C6, C8, and C9 hemolytic activities were unaffected. Concommitant with the loss of C3 hemolytic activity was the appearance of C3 proteolytic cleavage products that were identified by immunoelectrophoresis. Both the loss of C3 hemolytic activity and the production of C3 fragments occurred in the presence of 10 mM EDTA, indicating RCM-induced C3 cleavage occurred without participation of the multicomponent C3/C5 convertases of either the classical or alternative C pathways. Furthermore, loss of C3 hemolytic activity was not due to the direct alteration of the C3 molecule by RCM because purified C3 was unaffected upon incubation with RCM at a concentration that induced 80% reduction in the C3 hemolytic activity in normal human serum.
Serum samples obtained from 40 patients, before and 30 min after undergoing i.v. pyelography, revealed no significant change in total hemolytic C activity; 34 patients received sodium and methylglucamine diatrizoate and six received sodium iothalamate. Hemolytic C3 levels were also determined for the six patients before and 30 min after administration of sodium iothalamate and no significant change in activity was detectable.
Cytotoxic T Lymphocyte Sequential Killing of Immobilized Allogeneic Tumor Target Cells Measured by Time-Lapse Microcinematography
Authors: Rothstein Thomas L. , Mage Michael , Jones Gary , McHugh Louise L. 
Published: December 2022

Abstract
Sequential killing of allogeneic target cells by immune cytotoxic T lymphocytes (CTL) was directly observed by time-lapse microcinematography. Target cells (EL4 lymphoma cells from C56BL/6 mice), coated with Fab fragments of goat antibody to EL4, were immobilized by binding to the floor of a polystyrene tissue culture flask that had been precoated with specifically purified antigoat Fab. On adding immune BALB/c spleen CTL to such target cell monolayers it could be verified by direct observation that individual CTL could sequentially kill several target cells, that the CTL usually separated from the target cell before target cell death, that not all contacted target cells were killed, and that duration of contact was variable and not correlated with subsequent target cell death.
Regulation of Self Tolerance in Experimental Allergic Encephalomyelitis
Authors: Welch Andrew M. , Swierkosz James E. , Swanborg Robert H. 
Published: December 2022

Abstract
We studied the in vitro proliferative responses of lymph node cells (LNC) and spleen cells (SpC) from Lewis rats rendered unresponsive to experimental allergic encephalomyelitis (EAE) by pretreatment with guinea pig myelin basic protein (BP) in incomplete Freund's adjuvant (IFA). These LNC and SpC have suppressor function, since they protect cell recipients against EAE. LNC from unresponsive rats responded to Con A and PHA, indicating that T cell function was not nonspecifically impaired. In contrast, SpC responses were significantly suppressed. Mitogenic responses were restored by removing glass wool-adherent SpC. Moreover, when cocultured, SpC inhibited the LNC responses to Con A and PHA. Suppression of proliferative responses was again observed when normal peritoneal cells were added back to nonadherent SpC, suggesting that the suppressor SpC are macrophages. LNC and nonadherent SpC from unresponsive rats also responded in vitro to intact heterologous (guinea pig) BP, provided the rats had also been challenged with BP in complete Freund's adjuvant (CFA).
In contrast to the EAE suppressor LNC, which are nonadherent T lymphocytes, removal of adherent SpC abrogated adoptive transfer of unresponsiveness to EAE. These studies suggest that both antigen-specific suppressor T lymphocytes and nonspecific splenic adherent suppressor cells (presumably macrophages) may play a role in the maintenance of immunologic self-tolerance.
Null Cells in the Mouse Possess Membrane Immunoglobulins
Authors: Warr Gregory W. , Lee John C. , Marchalonis John J. 
Published: December 2022

Abstract
Null cells lacking typical T and B cell surface markers were isolated from the spleens of congenitally athymic mice by using either nylon wool or Sepharose macrobeads conjugated with rabbit antibody to mouse IgM to remove B lymphocytes. Although these null cells were negative for surface immunoglobulin by the criterion of immunofluorescence by using rabbit antisera to mouse heavy or light immunoglobulin chains, surface immunoglobulins were readily demonstrable by two alternative and independent techniques. First, by using chicken antibody to the (Fab′)2 fragment of mouse IgG, nearly all null cells were positive for immunofluorescence. Second, immunoglobulins could be detected in lysates of null cells radioiodinated by the lactoperoxidase-catalyzed reaction. Analysis of the surface immunoglobulins of null cells by radioimmunoassay and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate suggested that they are 1) qualitatively similar to those of B cells and 2) present in amounts between 10 and 30% of those of B cells.
Identification and Cytotoxic Reactivity of Inflammatory Cells Recovered from Progressing or Regressing Syngeneic UV-Induced Murine Tumors
Authors: Lill Patsy H. , William Fortner G. 
Published: December 2022

Abstract
Most tumors induced in C3H mice by ultraviolet (UV) light are immunologically rejected by normal syngeneic recipients, but will grow progressively in immunosuppressed mice and in mice treated with UV light. In this study we compared the composition and cytotoxic activity of the inflammatory cell infiltrate from tumors transplanted into syngeneic UV-irradiated or unirradiated mice. Tumor fragments were implanted in either normal (regressor) or UV-treated (progressor) mice, and removed on various days after implantation and mechanically dissociated. The cells were examined by immuno-fluorescence for θ and immunoglobulin markers, stained for morphologic examination, and tested for cytotoxicity against the tumor. No significant differences were noted in numbers of macrophages, granulocytes, or B cells recovered from progressing or regressing tumors on day 6, the time of greatest activity. However, the numbers of T cells recovered from tumor fragments implanted in normal mice was approximately 3-fold that recovered from tumor fragments implanted in UV-treated mice. Lymphocytes recovered from regressing tumor fragments were specifically cytotoxic for that tumor in a microcytotoxicity test; those from progressing tumor fragments were not cytotoxic.
Nonspecific Activation of Murine Lymphocytes
Authors: Goodman Michael G. , Fidler John M. , Weigle William O. 
Published: December 2022

Abstract
The lymphocyte subpopulations activated by 2-ME in C3H/St spleen cell cultures were characterized by means of kinetic and cell separation techniques. The current experiments were designed to determine whether 2-ME potentiates the maintenance of an activated state in cells that had been triggered by environmental stimuli encountered by the intact animal, or whether this thiol compound is able to transform typical resting lymphocytes to an activated state. Kinetic experiments demonstrated that the high rate of nucleotide turnover seen initially in cultured cells was not directly accentuated. Rather, this turnover was found to subside normally before 2-ME-initiated activation of lymphocyte [3H] TdR uptake began. Studies in which cells were separated according to sedimentation velocity showed clearly that 2-ME responsiveness is a quality of small lymphocytes (s = 3.9 mm/hr) and not of large, activated cells. Moreover, when cells were separated on the basis of buoyant density, reactivity to this thiol compound was found to reside within cells of high density, strongly supporting the thesis that 2-ME activates a resting lymphocyte subpopulation and does not simply maintain an activated state acquired in vivo. The influence of antigenic milieu was evaluated directly in mice reared under germfree, specific pathogen-free, and conventional conditions. Lack or limitation of environmental antigenic exposure resulted in a significantly larger DNA synthetic response to 2-ME. This pattern was presumed to reflect a greater preponderance of unstimulated lymphocytes in the spleens of germfree and SPF mice.
The Influence of α-Fetoprotein on Moloney Sarcoma Virus Oncogenesis: Evidence for Generation of Antigen Nonspecific Suppressor T Cells
Authors: Gershwin M. Eric , Castles James J. , Ahmed Aftab , Makishima Ronald 
Published: December 2022

Abstract
The influence of murine α-fetoprotein (AFP) on the threshold dose, mean tumor size, regression time, and number of progressors for Moloney sarcoma virus-(MSV) induced tumors in BALB/c mice was studied. AFP-treated mice developed larger tumors, required a longer period for regression, and had a significantly higher mortality. Furthermore, AFP, but not murine albumin or transferrin, allowed growth of tumors when normally subthreshold doses of virus were injected. These effects of AFP could be removed by pretreatment and precipitation of AFP by anti-AFP; on the other hand, they were not altered by dialysis and were noted at sera levels of approximately 170 to 440 µg/ml. The mechanism of this heightened susceptibility in AFP treated mice to MSV appears to be the generation of a cortisone, radiation sensitive splenic, and not lymph node, suppressor T cell. Indeed, the suppression produced by AFP was antigen nonspecific and could be demonstrated in unmanipulated mice after transfer of spleen cells from AFP-treated donors. This transfer of suppression was noted in IgG and IgA secondary responses to sheep red blood cells as well as by quantitating the response of T cell mitogens on spleen cells. These data suggest that AFP, in pharmacologic doses, either alters a subpopulation of spleen cells to exhibit suppressive function or else that AFP is involved in differential homing patterns of lymphoid cells. The relationships of AFP and immune competence appear broad and suggest the need for comparative studies with other oncofetal antigens.
Recognition by Cytolytic T and K Cells: Identification in Both Systems of a Divalent Cation-Independent, Cytochalasin A-Sensitive Step
Authors: MacLennan Ian C. M. , Golstein Pierre 
Published: December 2022

Abstract
Most studies of recognition events in cell-mediated cytolysis have analyzed the conditions that are required to establish mechanically stable binding between effector cells and target cells. This approach has shown that cytolytic T cells require a temperature above 20°C and free divalent cations to bind specifically to target cells. K cells on the other hand were shown to bind to IgG on target cells in the absence of divalent cations at 4°C. In this paper we shown that both K cell- and T cell-mediated cytolysis are inhibited by cytochalasin A, if this drug is added to cultures before the effector and target cells have interacted. However, the drug does not block the calcium-dependent lethal hit stage of cytolysis in either system. We then show that in both T cell- and K cell-mediated cytolysis, the cytochalasin A-inhibitable stage can proceed in the absence of divalent cations. We conclude from these data that: 1) both K cell- and T cell-mediated cytolysis have a divalent cation-independent stage, which is inhibitable by cytochalasin A; 2) firm mechanical binding of T effectors to target cells requires divalent cations. It is uncertain if the latter is necessary for cytolysis or whether K cells also have to go through a divalent cation phase before the lethal hit stage. The implications of these findings are discussed, especially as to the possibility that strong binding may not be necessary for T cell-mediated cytolysis.
Synergistic Cytotoxicity
Authors: Muchmore A. V. , Decker J. M. , Blaese R. M. 
Published: December 2022

Abstract
The mechanism by which non-immune mononuclear cells recognize invading foreign material and are activated for cytotoxic attack was studied in a model system employing human mononuclear cells, fresh plasma, and 51Cr-labeled xenogeneic target erythrocytes. In these experiments, fresh antibody-depleted plasma or mononuclear leukocytes alone were poorly cytotoxic to xenogeneic erythrocytes. However, these target cells were rapidly lysed when both fresh antibody-depleted plasma and mononuclear cells were present in the assay. The plasma factor could not be removed by extensive absorption with the target cells, was present in plasma from hypogammaglobulinemic patients, was heat labile, and was sensitive to incubation with zymosan and cobra venom factor. The “antigen” specificity of this reaction was directed by the serum factor inasmuch as target cells autologous to the effector cells could be killed in the presence of antibody-depleted xenogeneic plasma, but not autologous plasma. These data suggest that an important mechanism for the recognition of “foreignness” by non-immune mononuclear cells is via interaction with a plasma component, possibly a factor related to serum complement.
Immunoadjuvant Treatment of Primary Grafted and Spontaneous AKR-Leukemia
Authors: Olsson Lennart , Ebbesen Peter 
Published: December 2022

Abstract
Young AKR mice grafted i.v. with 101 or 103 cells from spontaneous AKR thymomas were treated with repeated i.v. injections of BCG or subcutaneous injections of irradiated AKR thymoma cells. BCG often cured mice from graft leukemia, whereas the effect of irradiated thymoma cells was less effective. Mice that did not develop graft-leukemia after graft of 101 leukemia cells and BCG treatment showed a spontaneous leukemia in 30% of the cases later. Ninety percent of nongrafted mice developed spontaneous leukemia whether BCG-treated or not. General immune reactivity as assessed in individual mice by T and B lymphocyte mitogen tests as well as the hemolytic plaque-forming cell assay had no clear correlation to the effects of immune adjuvants in respect to survival. In contrast, occurrence of self-directed immune reactions were clearly correlated to survival and cure of grafted and BCG-treated mice as revealed by assays both in vitro and in vivo. However, 13 to 25% of the mice apparently cured of leukemia developed a wasting-like syndrome that sometimes terminated in death. The implications of self-directed immune reactions as mediators of the anti-neoplastic effects of immunoadjuvants are discussed.
The Genetics of PLT Response
Authors: DeWolf William C. , Carroll Peter G. , Yunis Edmond J. 
Published: December 2022

Abstract
The primed lymphocyte test (PLT) has been used as a method to identify HLA-D or HLA-D-related (HLA-DRw) specificities; however, the assignment of HLA-D or HLA-DRw specificities by this procedure is often nondiscriminatory with false positive and false negative results. We have investigated three approaches to improve PLT discrimination: 1) restimulation of primed cells after various times in primary culture; 2) restimulation using a small number of responding PLT cells per well, and 3) nylon wool purification of responder cells before initial priming. The results show that when PLT cells are restimulated and the response is plotted on a log/log scale in relation to a decreasing number of responding cells per well, a characteristic “linear” relationship is seen when less than 1.0 × 104 PLT cells are used (stimulators = 5.0 × 104 cells per well). When greater than 1.0 × 104 PLT cells per well are used, a linear response is seen only when the priming culture is prolonged to 17 days or more. It is only when the PLT cell is in this “linear phase” of response that the responses to various stimulating cells can be compared to yield the most discriminatory % relative response (RR). Finally, nylon wool treatment of responder cells before sensitization improves subsequent discrimination in PLT when large numbers of primed responders per well are used. Thus, optimum discrimination in PLT is obtained: 1) by using a low number (less than 1.0 × 104) responding PLT cells per well, 2) by prolonging the priming MLC to at least 17 days, and 3) by pretreating the responder cells with nylon wool. These experiments suggest that during allogeneic stimulation in MLC, there is activation of a population of lymphocytes that react with HLA-D or HLA-DRw determinants and that other nonactivated or unprimed cells within the PLT population may alter a discriminatory response; such cells must be functionally decreased by these procedures for optimum results.
A Monoclonal IgG4 (λ) with Factor V Inhibitory Activity
Authors: Hurtubise Paul E. , Coots Macie C. , Jacob Donald J. , Muhleman Albert F. , Glueck Helen I. 
Published: December 2022

Abstract
A monoclonal IgG4 (λ) with inhibitory activity to human coagulation factor V was isolated from the serum of a patient with a fatal hemorrhagic diathesis by using a combination of DE-52 ion exchange chromatography and isoelectric focusing techniques. Using the criteria for defining a monoclonal immunoglobulin of restricted mobility on protein electrophoresis, immunoelectrophoresis, and isoelectric focusing, as well as neutralization with class, subclass, and light chain type antisera, we are the first to demonstrate a factor V inhibitor as a monoclonal IgG4 (λ) detectable in serum or plasma.
Release of Immature Cells from the Thymus during Solid Tumor Growth: Identification by Assay of TdT Activity
Authors: Small Myra , Lasser-Weiss Meira , Daniel Violet 
Published: December 2022

Abstract
In vivo anti-tumor activity of spleen cells from C3H/eb mice bearing a syngeneic fibrosarcoma was shown previously to decline to an undetectable level and be replaced by tumor-enhancing activity as tumor growth proceeds. In the light of our findings that thymocytes in the early stages of thymic processing can bring about tumor enhancement, we postulated that premature release of thymocytes and their accumulation in the spleen might account for the loss of the anti-tumor response. In the present experiments an injection of thymocytes did in fact cancel the anti-tumor response of reactive splenocytes from tumor-bearing mice. In order to determine whether premature thymocyte release occurs naturally in the tumor-bearing animals, we assayed activity of the enzyme TdT (as a marker for thymus cells) in the spleens of these mice during progressive tumor growth. Cells with TdT activity were clearly evident in the spleens of the tumor-bearing animals, were derived from the thymus, and accumulated in parallel to the loss of antitumor reactivity.
Cytotoxic Macrophages Induced in Hamsters by Vaccinia Virus: Selective Cytotoxicity for Virus-Infected Targets by Macrophages Collected Late After Immunization
Authors: Chapes Stephen K. , Tompkins Wayne A. F. 
Published: December 2022

Abstract
Peritoneal macrophages from LHC/Lak hamsters infected with vaccinia virus were tested for cytotoxicity against uninfected and vaccinia or herpes simplex virus-infected semiallogeneic target cells (BHK and PARA-7) in a 51Cr cytotoxicity assay. Macrophages were tested between 3 and 34 days after immunization of hamsters with 1 × 107 PFU of vaccinia virus. Peak cytotoxicity against BHK infected with vaccinia virus (BHKV) or herpes simplex virus (BHKH) occurred at 5 days after immunization and declined to baseline by 34 days. At no time after immunization was there evidence of preferential killing of the specific BHKV targets. However, macrophages tested 3 to 5 days after immunization differed from those tested later, both in their kinetics of cytotoxicity and the type of target cell recognized. Thus, 5-day immune macrophages were cytotoxic for uninfected BHK and PARA-7 hamster tumor cells as well as BHKV and BHKH. In contrast, 9-day immune macrophages were cytotoxic for BHKV and BHKH, but not uninfected BHK or PARA-7. Also, in vitro assay kinetics showed that early 5-day immune macrophages were more rapidly cytotoxic for all target cells than late 9-day immune macrophages. This study also showed that nonadherent peritoneal exudate cells (NPEC) were induced by vaccinia immunization that were nonspecific in their cytotoxicity. Although both adherent macrophages and NPEC showed preferential lysis of virus-infected targets, the cytotoxicity mediated by NPEC was abrogated by treatment with NH4Cl, whereas macrophage cytotoxicity was not affected by such treatment. In summary, this study demonstrates that with time after immunization with vaccinia virus peritoneal macrophages differ markedly in their cytotoxicity characteristics with respect to target cell recognition and rate of target cell killing. Possible models to explain preferential cytotoxicity against virus-infected targets by late vaccinia immune macrophages are discussed.
Surface Properties and in vitro Functional Capacities of Human T Lymphocyte Subsets Separated by Linear Density Gradients
Authors: Huber Christoph , Rodt Hans , Thierfelder Stefan , Braunsteiner Herbert 
Published: December 2022

Abstract
Human lymphocytes derived from various central and peripheral sources were separated on linear density gradients (LDG). Cells from individual density fractions were tested in parallel for: the capacity to form nonimmune rosettes with neuraminidase-treated SRBC, the number of surface-associated HTLA, and in vitro proliferative responses to mitogenic lectins and alloantigens.
Heterogeneous density distribution profiles were obtained for all sources of human T cells and revealed an organ specificity. The various T cell density classes obtained from identical organs as well as the identical density classes of different sources revealed to some extent differences in their surface marker patterns and/or their in vitro reactivities. On the basis of the combined techniques at least two major subsets among thymocytes were identified that differed in both surface properties and functional capacities. Density classes of T cells from all peripheral sources were distinguished from thymocytes by a homogeneous lowered HTLA expression. Whereas clear-cut differences in the in vitro functional capacity were observed between the two thymocyte subsets, less striking but still significant differences were found to exist among the various density classes of peripheral T cells.