bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel type of human T cell clone with highly potent natural killer-like cytotoxicity divorced from large granular lymphocyte morphology.
Authors: Schneider E M , Pawelec G P , Liangru S , Wernet P 
Published: December 2022

Abstract
Interleukin 2-dependent cloned lymphocytes derived from an allogeneic HLA class II-mismatched but class I-matched mixed lymphocyte culture were screened for cytotoxic activity on target cell lines known to be susceptible or resistant to lysis by natural killer (NK) cells. Of 24 clones, eight were found to display NK-like cytotoxicity. Two manifested extremely high cytotoxicity levels (50% lysis of K562 at an effector to target ratio of 1:1), whereas the remainder were only moderately active (about 20% lysis at 25:1). NK-like clones were studied with regard to cell surface markers defined by monoclonal antibodies, as well as for their morphologic and cytochemical characteristics, and were compared with clones displaying different functions. The moderately active NK-like clones exhibited characteristic large granular lymphocyte morphology (many azurophilic granules, indented nuclei, high cytoplasm to nucleus ratio, and a basophilic peripheral cytoplasmic zone). This was, however, also characteristic of the majority of lymphocyte clones displaying functions other than NK. Surprisingly, the two clones with high NK-like activity did not exhibit large granular lymphocyte morphology, with few granules, round nuclei, and low cytoplasm to nucleus ratio. The T3, T9, T10, and T11 markers, as well as HLA-DR determinants, were expressed on their surfaces, but in contrast to the other clones, they did not display OKT4-, OKT8-, or OKM1-defined antigens. No distinction between them was possible on the basis of a cytochemical profile in relation to their function, because all clones were positive for acid phosphatase, either focal or dispersed and negative for nonspecific esterase or chloracetate esterase. The highly active lytic clones were, however, distinguished by an exceptionally rapid growth rate in culture (cell doubling time: 9 hr as compared to 30 to 40 hr, as usually required). These results demonstrate two different types of human NK-active lymphocytes with remarkably disparate lytic capacity, cell surface markers, and morphology.
The antigen of mature human B cells detected by the monoclonal antibody FMC7: studies on the nature of the antigen and modulation of its expression.
Authors: Zola H , Moore H A , Hohmann A , Hunter I K , Nikoloutsopoulos A , Bradley J 
Published: December 2022

Abstract
The monoclonal antibody FMC7 delineates a subpopulation of B lymphocytes in normal blood. Expression of the antigen recognized by FMC7 appears to be maturation-linked, and it serves to distinguish different types of B cell leukemia. The data presented here indicate that the antigen is a protein that is integrated in the cell membrane and that is able to interact with the cytoskeleton. The antigen is rapidly synthesized and turned over, is not cell cycle-dependent, and is relatively resistant to changes induced by culture in the presence of a phorbol ester.
Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus. I. Generation and recognition of virus strains and H-2b mutants.
Authors: Byrne J A , Ahmed R , Oldstone M B 
Published: December 2022

Abstract
Cytotoxic T lymphocytes (CTL) were induced in C57BL/6 and (C57BL/6 X DBA/2)F1 mice after immunization with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV-Arm) and were cloned by limiting dilution in vitro. The cytotoxic activity of these clones was LCMV specific and H-2 restricted. All clones induced in C57BL/6 (H-2b) mice with LCMV-Arm lysed target cells infected with each of five distinct strains of LCMV (Arm, Traub , WE, Pasteur, and UBC ), suggesting recognition of common regions of viral proteins in association with H-2b molecules. In contrast, one clone obtained from (B6 X D2)F1 mice and restricted to the H-2d haplotype only lysed cells infected with one of three strains of virus (Arm, Traub , WE) but not two others (Pasteur, UBC ), suggesting recognition of variable regions of viral proteins in the context of H-2d molecules. To assess the fine specificity for H-2 molecules, we tested H-2Kb-restricted CTL clones for their ability to kill LCMV-infected target cells bearing mutations in their H-2Kb, and we tested clones presumed to be restricted to the H-2Db region for their ability to all LCMV targets cells bearing a mutation in the H-2Db region. Several different patterns of killing of the mutant targets were observed, indicating that a number of different epitopes on the H-2b molecules were used as restricting determinants for LCMV antigen recognition by CTL. Thus, cross-reactive viral determinants were recognized in the context of several different restricting determinants. Mutations in the N or C1 domains of the H-2 molecule affected recognition by a single LCMV specific CTL clone. One implication of this result is that CTL recognize a conformational determinant on the H-2 molecule formed by the association of virus antigen(s) with H-2. An alternate explanation is that one site on the H-2 molecule is involved in the interaction of viral antigens with H-2, whereas another may serve as a binding site for the CTL receptor.
Early loss of precursors of CTL and IL 2-producing cells in the development of neonatal tolerance to alloantigens.
Authors: Carnaud C , Ishizaka S T , Stutman O 
Published: December 2022

Abstract
Bulk culture and limiting dilution analysis (LDA) were used to follow the ontogeny of the tolerant state in CBA/ HT6T6 mice neonatally tolerized to allogeneic histocompatibility antigens. Advantage was taken of the fact that the lymph nodes (LN) of young mice show immunocompetence before spleen cells do, allowing analysis of actual reactivity as early as 1 wk of age. At 1 wk, the LN cells of mice tolerized i.v. showed a loss of CTL reactivity in bulk culture specific for the tolerizing antigens; a corresponding specific decrease was seen in the frequency of CTL precursors (CTLp). At the same age, however, proliferative responses and interleukin 2 (IL 2) production in MLC were nonspecifically depressed in the tolerized animals. LDA of IL 2 producer precursor frequency (IL- 2Tp ) showed that there was a nonspecific loss of 50% of functional alloreactive IL- 2Tp , accompanied by a larger specific decrease of 90% in the frequency of IL- 2Tp responding to the injected alloantigens. These characteristics of the tolerant state persisted through at least 4 wk of age. Neither the proliferative nor CTL response deficiencies could be overcome by the addition of Con A supernatant containing IL 2. Mixing experiments failed to show evidence of suppressor cell involvement in the loss of the proliferative response. Our results indicate that the specific loss of alloreactivity after tolerization is due to clonal inactivation or deletion of both CTLp and IL- 2Tp , which is obvious as early as 7 days of age. In addition, the differences in the specificity of the clonal inactivation between CTLp and IL- 2Tp suggest the existence of independent mechanisms for tolerization.
Susceptibility of inbred mice to Leishmania tropica infection: genetic control of the development of cutaneous lesions in P/J mice.
Authors: Fortier A H , Meltzer M S , Nacy C A 
Published: December 2022

Abstract
Leishmania tropica infections of P/J mice are characterized by the development of progressive nonhealing cutaneous lesions, followed by visceral metastases to liver and spleen. To analyze the genetic control of this disease, we produced F1, backcross (BX), and F2 progeny by breeding susceptible P/J mice with L. tropica-resistant C3H/HeN mice. Infections in these hybrid animals suggested that genetic control of the cutaneous lesion was by a single, autosomal, dominant gene. Resistance was the dominant trait. Analysis of liver and spleen impression smears in these animals, however, indicated that development of the cutaneous lesion segregates independently of the second component of L. tropica infections, systemic disease.
Blocking activity of rat monoclonal antibodies in experimental schistosomiasis.
Authors: Grzych J M , Capron M , Dissous C , Capron A 
Published: December 2022

Abstract
Rat IgG2c monoclonal antibodies have been produced after fusion of spleen cells from LOU/C rats infected with Schistosoma mansoni for 5 wk and IRF983F nonsecreting rat myeloma. The cell supernatant of an IgG2c-producing clone (IPLSm3), as well as ascitic fluids induced by this clone, revealed anti-S. mansoni activity detected by immunofluorescence on schistosomula sections. Antigenic analysis performed with IPLSm3 IgG2c antibody allowed to isolate onto the S. mansoni schistosomula surface a 38,000 dalton antigen previously characterized with the protective IPLSm1 IgG2a monoclonal antibody. Although IPLSm3 IgG2c did not exhibit any killing activity in vitro against schistosomula in the presence of complement, macrophages, or eosinophils, it was shown to strongly inhibit the eosinophil-dependent cytotoxicity mediated by IPLSm1 IgG2a antibodies. The blocking activity of IgG2c antibody was further demonstrated in vitro by the use of F(ab')2 fragments and in vivo by the inhibition of passively transferred immunity conferred by the IgG2a protective monoclonal antibody. These results indicate that blocking antibodies could play an important role in the expression of protective immunity during schistosome infection.
CTL recognize different determinants from those defined serologically on Ld somatic cell mutants.
Authors: Bluestone J A , Potter T A , Chatterjee-Hasrouni S , Rajan T V 
Published: December 2022

Abstract
Reciprocal Ld structural mutants have been isolated from a somatic cell line. Testing of allogeneic CTL clones on these mutants suggests that the majority of CTL clones recognize determinants different from those that elicit antibody production. Of 36 CTL clones tested, only three clones appeared to recognize a determinant that was related to the negatively selected serologic determinant. However, mAb blocking studies suggest that inhibition of CTL activity by anti-H-2 mAb does not necessarily reflect the fine specificity of the CTL activity.
Differences in delayed-type hypersensitivity responses in various mouse strains in the C3H lineage infected with Salmonella typhimurium, strain SL3235.
Authors: Killar L M , Eisenstein T K 
Published: December 2022

Abstract
Immunization with a virulent Salmonella typhimurium, strain SL3235, has been found to provide high levels of protection against challenge with virulent Salmonella in hypersusceptible mouse strains in the C3H lineage. These mouse strains include the lipopolysaccharide-hyporesponsive C3/HeJ mouse and the closely related but lipopolysaccharide-responsive C3HeB/FeJ mouse. To assess the role of cellular immunity in the protection elicited by this attentuated organism, delayed-type hypersensitivity (DTH) was measured in these mouse strains and in inherently resistant mice. Of the mouse strains tested, only the inherently resistant CD-1 and C3H/HeNCrlBR mice developed significant DTH responses, as assessed by footpad swelling tested at various times after immunization with SL3235. The hypersusceptible C3H/HeJ and C3HeB/FeJ mice failed to exhibit significant DTH responses despite their high levels of immunity.
Antigen-specific T helper clones in a nonresponder strain require augmentation for expression of helper activity. Evidence for a possible antigen presentation defect in B cells.
Authors: Shastri N , Kawahara D J , Miller A , Sercarz E E 
Published: December 2022

Abstract
Hen egg-white lysozyme (HEL)-specific Thy-1+, Lyt-1+2- T cell lines and clones were derived from the nonresponder C57BL/6 strain. Although the antigen-specific proliferative response of these T cells in the presence of syngeneic irradiated spleen cells as a source of antigen-presenting cells (APC) was normal, the same cells were incapable of stimulating B cells to secrete antibody in vitro. This deficiency could, however, be corrected by the addition of an excess of normal T cells or a supernatant from concanavalin A-stimulated rat spleen cells. Alternatively, the use of highly cross-reactive ring-necked pheasant lysozyme in the cultures allowed expression of efficient help, ruling out any inherent deficiency in the T cells. The antibody response was specific and required MHC compatibility between the T lines and responding B cells. By using (H-2b X H-2d)F1 B cells and another H-2d-restricted HEL-specific T line, it was shown that only the H-2b-restricted T-B collaboration required exogenous factors, and the H-2d-restricted collaboration did not. Because both proliferative and helper responses are dependent upon MHC-restricted antigen presentation by macrophage-APC and B cells, respectively, these results suggest that the defect in the nonresponder H-2b-restricted T-B collaborative pathway may relate to the inability of B cells to adequately process and present HEL to clonal T cells.
Human T cell clones exerting multiple cytolytic activities show heterogeneity in susceptibility to inhibition by monoclonal antibodies.
Authors: van de Griend R J , Giphart M J , Van Krimpen B A , Bolhuis R L 
Published: December 2022

Abstract
Human cytotoxic T cell clones (CTL) were obtained by limiting dilution after in vitro priming against an allogeneic Epstein Barr virus (EBV)-transformed B cell line (B-LCL) BSM. Three OKT3+, OKT8+ E rosette-forming (RFC) but EA gamma-RFC- clones with cytotoxic activity against the stimulator cell and one "non-cytolytic" clone were expanded for over 50 generations and further characterized. Clone G9 showed allospecific lysis of Cw3+ lymphocytes and B cell lines. Three cytolytic clones (G9, D11, and A3) showed cytotoxicity to the stimulator B-LCL, to the human plasma cell leukemia-derived line LICR-LON-HMY2 and to short-term cultured melanoma cells (O-mel). Four other EBV-transformed B-LCL unrelated to the stimulator B-LCL were not lysed. These clones also exerted cytotoxic activity against NK-sensitive target cells (TC), e.g., the erythroleukemia cell line K562. Other NK-sensitive TC, e.g., lymphoma-derived Daudi cells, were killed provided they were pretreated with phytohemagglutinin (PHA). Cytolytic activity against the B-LCL cell LICR-LON and O-mel, but not against K562 or PHA-treated target cells, was inhibited by monoclonal anti-HLA ABC antibodies (MCA). The cytolytic activities of OKT3+,8+ clones G9 and A3 but not that of OKT3+,8+ clone D11 were inhibited by OKT8. Another MCA, 13.3, directed against the murine glycoprotein T-200, inhibited the cytolytic activity of clone D11 against K562 but not against the stimulator cells. Clone G9 was not inhibited by MCA 13.3. The four clones, including the OKT4+ "non-cytotoxic" clone K12, exerted lytic activity against TC that are normally resistant to lysis provided these TC were pretreated with PHA. The TC specificity range of the clones was confirmed by cold target inhibition experiments. A correlation between blocking of lytic activity by cold TC and the percentage of conjugate formation with the particular cold TC was observed. Because these clones also show differential susceptibility to inhibition of lysis by various MCA, it is concluded that human cytotoxic T cell clones can exert multiple lytic activities, i.e., the operationally defined lytic mechanisms differ at least at certain stages of the lytic cycle.
In vitro generation of human activated lymphocyte killer cells: separate precursors and modes of generation of NK-like cells and "anomalous" killer cells.
Authors: Burns G F , Triglia T , Werkmeister J A 
Published: December 2022

Abstract
The activation of human peripheral blood mononuclear cells (PBM) in culture leads to the generation of nonspecific killer cells. These cells, termed activated lymphocyte killer (ALK) cells, can kill fresh tumor cells and tumor cell lines, in addition to the natural killer (NK) cell sensitive target K562. ALK cells have features in common with both T and NK cells, but their nature and origin are unknown. In the present study, it is shown that ALK cells are in fact heterogeneous and can be generated from both large granular lymphocytes with the same phenotype as NK cells and from T cells. Cell populations enriched for NK cells, when cultured with lymphokines, rapidly acquired a T cell phenotype, enhanced cytolytic activity against K562, and the ability to lyse NK-insensitive target cells such as a melanoma cell line LiBr; these ALK cells were described as NK-like cells. On the other hand, of the cloned cells derived from PBM stimulated with irradiated B lymphoblasts and grown in lymphokines, the major proportion of cytolytic T cells (CTC) able to kill the specific stimulator lymphoblasts were also found to kill LiBr but not K562 cells. These ALK cells, which were derived from the same precursors as CTC, were designated anomalous killer (AK) cells. Consistent with this, the presence of the pan T monoclonal antibody UCHT1 from the beginning of mixed cell cultures inhibited the generation of CTC and of the AK-type of ALK cell, which killed melanoma cells, but not the NK type, which killed K562 targets. By contrast, at the effector cell level, the antibodies UCHT1 and OKT8 only blocked specific killing by CTC but did not block the killing of LiBr or of K562 targets by ALK cells. However, at the effector cell level there was additional evidence for the heterogeneity of ALK cells. Thus, monoclonal antibody 9.1C3, which blocks killing by freshly isolated NK cells, also blocked the killing of K562 targets by NK-like cells, but did not block B lymphoblast killing by CTC or melanoma cell killing by AK cells. It is concluded that after mixed lymphocyte culture, the majority of ALK cells measured by the killing of melanoma target cells arise from the same precursors and are under the same influences as classical CTC (AK cells), whereas cells killing K562 targets are derived from NK cells (NK-like cells). Once generated, the AK cells have a different mechanism of killing from both classical CTC and from NK and NK-like cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.
Authors: Gerdes J , Lemke H , Baisch H , Wacker H H , Schwab U , Stein H 
Published: December 2022

Abstract
The monoclonal antibody Ki-67 detects a nuclear antigen that is present only in proliferating cells. The aim of the present investigation was to clarify whether the Ki-67 nuclear antigen is restricted in its expression to certain phases of the cell cycle. All experiments consistently showed that the Ki-67 nuclear antigen is present in S, G2, and M phase, but is absent in G0. However, the results concerning Ki-67 antigen expression in G1 phase varied: cells passing the early events of mitogen triggered transition from G0 to G1, i.e., G1T and first G1A, lacked the Ki-67 nuclear antigen, whereas G1 cells after mitosis were constantly Ki-67-positive. This result suggests that after mitosis cells might not follow the same metabolic pathways as G0 cells do when entering G1 for the first time. Therefore, we suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle. Because our data show that the Ki-67 nuclear antigen is present throughout the cell cycle, immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.
Studies on the mechanism of suppression of primary cytotoxic responses by cloned cytotoxic T lymphocytes.
Authors: Fink P J , Rammensee H G , Benedetto J D , Staerz U D , Lefrancois L , Bevan M J 
Published: December 2022

Abstract
We have shown in the accompanying companion paper that cloned cytotoxic T lymphocytes (CTL) can serve as veto cells in vitro, suppressing primary cytotoxic activity directed against antigens expressed by those cloned CTL but not against third party antigens. We now explore the mechanism of this antigen-specific suppression by cloned CTL, using as a model system the ability of G4, a BALB.B anti-H-2Dd CTL clone, to specifically suppress a primary in vitro anti-H-2b CTL response. G4 cells do not constitutively secrete a suppressor factor, because suppression cannot be mediated by supernatants removed from G4 cells at a time when they are routinely used as veto cells. Furthermore, medium removed from cultures suppressed by G4 will not suppress, indicating that the veto cell function of G4 is not mediated by soluble factors. Full suppression of primary anti-H-2b CTL responses requires that G4 be present throughout the 5-day mixed lymphocyte culture (MLC). Removal of G4 during the first 3 days of MLC results in a drastic reduction in the level of antigen-specific suppression, with a slight but reproducible loss of suppression after veto cell removal on day 4. The addition of G4 during the course of an ongoing MLC reveals that maximal suppression requires the presence of veto cells during the first 24 to 48 hr of culture. Thus, G4 cells must be present both early and late in an MLC to exert maximal veto cell suppression. Several experiments suggest that G4-induced veto cell activity is unlikely to be due to cytolysis of CTL precursors which are capable of recognizing G4. G4 cannot specifically recognize these CTL precursors, and G4 cells are inefficient at lectin-mediated lysis of non-tumor cell targets. Furthermore, we show that G4 cells cannot lyse CTL which recognize them. Finally, dilutions of anti-clonotypic antibodies which completely block both lectin-mediated and specific cytolysis by G4 do not block (and in fact enhance) G4-mediated veto cell activity.
Major histocompatibility antigens are not detectable on post-meiotic human testicular germ cells.
Authors: Anderson D J , Narayan P , DeWolf W C 
Published: December 2022

Abstract
Neither HLA Class I nor Class II transplantation antigens were detected on human testicular germ cells by immunohistologic or immunoprecipitation techniques. This unusual characteristic of human germ-line cells could help to explain their immunologically privileged status in potentially hostile autologous and allogeneic host environments.
The suppression of insulin-specific immune responses by the administration of insulin-derivatized syngeneic cells and soluble lysates from these cells.
Authors: Kudo K , Stefura W P , Miyamoto M , Yoshida T , Sehon A H , Schwenk R J 
Published: December 2022

Abstract
The results of this study demonstrated that the i.v. administration of insulin, in the form of a conjugate with either syngeneic spleen cells (SC) or peritoneal exudate cells (PEC), markedly reduced the capacity of recipient mice to develop insulin-specific immune responses, as manifested by diminished in vivo IgE antibody production and by depressed in vitro, lymph node cell proliferation responses, respectively. Furthermore, it was shown that i.v. injection of insulin-PEC conjugates induced the activation of suppressor cells that had the capacity to downregulate insulin-specific IgG plaque-forming cell (PFC) responses. Finally, it was also determined that freezing and thawing of the insulin-PEC conjugates resulted in the release of a soluble tolerogenic molecule and/or membrane preparation that could also markedly depress insulin-specific IgG antibody production.