bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+ T cell-mediated killing of MHC class II-positive antigen-presenting cells. I. Characterization of target cell recognition by in vivo or in vitro activated CD4+ killer T cells.
Authors: Erb P , Grogg D , Troxler M , Kennedy M , Fluri M 
Published: December 2022

Abstract
Ag-specific as well as Ia-restricted killing of certain APC by CD4+ T cells was investigated. The CD4-mediated killing is not only a characteristic of in vitro long term cultured T cell lines or clones, but is also manifest after in vivo priming. Thus, CD4+ killer T cells are generated in vivo as well. CD4+ killer T cells are detected in the Th1, but not in the Th2 subset, and they do not appear to lyse Ia+ APC or bystander cells by a pathway mediated by secreted T cell factors. The latter observation is demonstrated by cold target inhibition experiments as well as by the failure of puromycin to inhibit killing, if applied in doses which completely block lymphokine secretion. Ia+ APC differ in their susceptibility to lysis. Transformed APC are usually better lysed than nontransformed APC. Unstimulated B cells are not killed, while LPS-stimulated B cell blasts are killed. The results of cold target inhibition and bystander killing experiments suggest that CD4+ killer T cells are activated by the common pathway, i.e., by Ag presented in the context of Ia, but killing requires the recognition of additional determinant(s) on APC. It is proposed that these killing-inducing determinants are continuously expressed on most transformed Ia+ cells and on nontransformed but stimulated APC.
A novel homodimeric molecule involved in human T cell activation.
Authors: Kobata T , Yagita H , Matsuda H , Tansyo S , Yakura H , Katagiri M , Okumura K 
Published: December 2022

Abstract
A mAb, 10D1, was obtained by fusing spleen cells from BALB/c mice immunized with a CD3/TCR- human T cell line, P12/ichikawa, to mouse myeloma cells, P3X63-Ag8-653. 10D1 mAb is specific for T cells in that it reacted with all the T cell lines tested, but not with B or myeloid cell lines. A small fraction of normal peripheral blood T cells, preferentially CD4+, was also reactive with 10D1 mAb. Biochemical studies revealed that 10D1 mAb recognizes a disulfide-linked homodimeric molecule composed of 90-kDa polypeptide. 10D1 mAb induced a substantial proliferation of peripheral blood T cells when cross-linked with goat anti-mouse Ig antibody. The elimination of CD4+ cells totally abrogated the proliferative response induced by 10D1 mAb, whereas the elimination of CD8+ cells rather enhanced it. The proliferative response of peripheral blood T cells induced by 10D1 mAb was almost completely inhibited after modulation of the CD3/TCR complex with anti-CD3 mAb. In addition, a prompt increase in intracellular [Ca2+] was observed in a CD3+ T cell line, Jurkat but not in its surface CD3- mutant when 10D1 mAb was added. These results indicate that the 10D1 molecule is involved in a novel pathway of human CD4+ T cell activation, which is associated with the CD3/TCR-mediated pathway.
Bacterial proteins that mediate the association of a defined subset of T cell receptor:CD4 complexes with class II MHC.
Authors: Yagi J , Baron J , Buxser S , Janeway C A 
Published: December 2022

Abstract
We have examined the responses of cloned T cell lines and of normal T cells to staphylococcal enterotoxins A, B, and C1 (SEA, SEB, and SEC1). SEA, SEB, and SEC1 are all very potent mitogens for T cells in the presence of Ia+ APC. The minimal activating dose of all these SE varies from 1 to 100 ng/ml. As determined by mAb blocking of the responses of both normal T cells and cloned T cell lines, SEA required either the I-A or the I-E molecule on APC for stimulating T cells, whereas SEB required the I-E molecule predominantly over I-A molecule. The TCR:CD4 complex is also involved in the response to SE. The responses to SEB and SEC1 were inhibited by anti-V beta 8 antibody F23.1, whereas the response to SEA and to PHA was not affected by this antibody. Anti-CD4 effectively inhibited responses to all SE but not to PHA. The involvement of the TCR was also confirmed by flow microfluorimetry analysis of T cell blasts responding to SE and the responses of a panel of cloned T cell lines, both of which showed that V beta 8+ T cells preferentially responded to SEB, whereas V beta 8+ T cells failed to respond to SEA. By using fixed APC, it could be shown that processing is not required for the presentation of SE. Furthermore, pulsing experiments showed that SEB can bind to relevant sites on either B cells or T cells, whereas with conventional Ag only prepulsing of the APC has worked. In one case, SEB activates a cloned T cell line in the absence of APC, and this same clone also responds directly to anti-V beta 8 antibody. Thus, SEB appears to bring together V beta 8-expressing TCR with the I-E molecule, whereas SEA apparently has the same effect on TCR expressing different V beta with either the I-A or the I-E molecule, probably depending upon which TCR is bound. The close resemblance between T cell responses to SE and those to mixed-lymphocyte stimulating (Mls) locus suggests to us that a novel SE-like protein that binds both to class II MHC molecules on the APC surface and to V beta gene products on TCR could be the product of the Mls locus.
Abnormal thymocyte maturation in spontaneously diabetic BB rats involves the deletion of CD4-8+ cells.
Authors: Plamondon C , Kottis V , Brideau C , Métroz-Dayer M D , Poussier P 
Published: December 2022

Abstract
The object of this study was to further characterize the pathophysiology of the peripheral T lymphopenia in the BB rat. Towards this end, surface markers on unseparated thymocytes and purified thymocyte subsets from age- and sex-matched diabetes-resistant (BBn) and diabetes-prone (BBd) rats were analyzed by two-color flow cytometry. The proportions of thymocytes falling into each of the four main phenotypic subsets were comparable in BBn (n = 9) and BBd (n = 8) rats: respectively, 4.6 +/- 0.6% and 4.4 +/- 0.8%, CD4-8-; 68.1 +/- 1.9% and 71.1 +/- 3.2%, CD4+8+; 18.3 +/- 1.5% and 15.4 +/- 2.3%, CD4+8-; 9.1 +/- 0.9% and 9.1 +/- 1.0%, CD4-8+. In addition, absolute numbers of thymocytes were not significantly different. The levels of expression of CD4, TCR-alpha beta within each thymocyte subset were comparable in BBn and BBd animals as were the anti-TCR-induced proliferative responses of their CD4+8- and CD4-8+ thymocytes. However, phenotypic abnormalities within the CD4-8+ thymocyte subset of the BBd rat were found. A very significant (p less than 0.005) deletion of mature CD4-8+, TCR-alpha beta + thymocytes and a proportional increase (p less than 0.005) of immature CD4-8+, TCR-alpha beta low thymocytes. Moreover, a twofold decrease of CD8 expression by mature CD4-8+ thymocytes was observed in BBd animals. These results suggest that an impaired thymic maturation contributes to the peripheral T lymphopenia of the BBd rat.
The leukocyte adhesion glycoprotein CD18 participates in HIV-1-induced syncytia formation in monocytoid and T cells.
Authors: Valentin A , Lundin K , Patarroyo M , Asjö B 
Published: December 2022

Abstract
mAb 60.3 and IB4 to CD18, the common beta-subunit of the human leukocytic cell adhesion molecule family, efficiently inhibit syncytium formation induced by the interaction of HIV type 1 (HIV-1)-infected monocytoid cells and CD4+ T cells. The antibodies also interfere with cellfree HIV-1 infection of U-937 clone 16 cells. Virus-induced aggregation of these cells and the subsequent syncytia formation leading to massive cell death are efficiently blocked, and the number of infected cells remains at a very low level, 2 to 5%, for the entire culture period. However, anti-CD18 mAb do not inhibit binding of the viral envelope glycoprotein gp120 to the cell surface receptor CD4. The results indicate participation of CD18, or of the protein complex CD11a-c/CD18, in addition to CD4, in the infection and cytopathic effect of HIV-1. They also suggest that intercellular adhesion contributes to virus transmission from cell to cell and may be an important mechanism for virus spreading.
Competition between foreign and self proteins in antigen presentation. Ovalbumin can inhibit activation of myelin basic protein-specific T cells.
Authors: Gautam A M , Glynn P 
Published: December 2022

Abstract
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory neurological disease initiated by activated T cells specific for the autoantigen, myelin basic protein (MBP). The ability of Lewis rat splenic T cells to transfer EAE after in vitro incubation with MBP-pulsed dendritic cells (DC) was used as an index of MBP-specific T cell activation. OVA, previously processed by macrophages, was incubated with MBP and DC at the pulsing stage to determine whether it could inhibit presentation of the autoantigen. At molar equivalents of 2.5:1 and 20:1 relative to MBP, processed OVA increasingly inhibited the ability of DC to activate MBP-specific T cells for EAE transfer. Unprocessed OVA, which cannot be presented immunogenically by Lewis rat DC, was much less effective. However, processed OVA added to DC after they had been pulsed with MBP could not compete. OVA also blocked appearance of EAE when mixed with MBP/CFA in the inoculum used for active induction of the disease. Splenic T cells from MBP + OVA/CFA-immunized rats transferred EAE with a substantially delayed onset, suggesting that a reduced number of MBP-specific T cells was generated by immunizing with the OVA + MBP mixture compared with MBP alone. Overall, the data indicate that fragments of a foreign protein, OVA, which can be bound by APC, can also inhibit presentation of encephalitogenic determinants of MBP to T cells.
Activation of MHC class I-restricted CD8+ CTL by microbial T cell mitogens. Dependence upon MHC class II expression of the target cells and V beta usage of the responder T cells.
Authors: Herrmann T , Maryanski J L , Romero P , Fleischer B , MacDonald H R 
Published: December 2022

Abstract
The T cell response to microbial T cell mitogens (MTM) such as enterotoxins from Staphylococcus aureus (SE) and the soluble mitogen from Mycoplasma arthritidis, resemble the minor lymphocyte stimulatory locus (Mls) response in several aspects. An important feature of the Mls response is it restriction to CD4+ cells. This study demonstrates that in contrast to Mls, the MTM response includes both CD4+ and CD8+ subsets. Both CD4+ and CD8+ cells expanded in IL-2 after stimulation with SEB showed preferential expression of T cell receptors bearing V beta 8 domains. Mouse and human target cells could be lysed in the presence of MTM both by MTM-stimulated CD8+ lymphocytes and by MHC class I-restricted CTL clones of defined Ag specificity. MTM-induced lysis required the expression of MHC class II, but not class I Ag, on the target cells. Inhibition studies of SEB and Ag-dependent cytolysis by CTL clones underlined the crucial role of CD3 and LFA-1 in both instances, but showed CD8 dependence only for AG-dependent cytolysis. Together these findings suggest important differences between the putative MTM-mediated interaction of TCR with MHC molecules and the classical TCR/MHC interaction involved in MHC-restricted Ag recognition.
Functional CD2 mutants unable to bind to, or be stimulated by, LFA-3.
Authors: Wolff H L , Burakoff S J , Bierer B E 
Published: December 2022

Abstract
To define epitopes on the CD2 (T11, the T cell erythrocyte receptor) molecule that are necessary for interaction with lymphocyte function-associated Ag-3 (LFA-3), we have expressed the human wild-type CD2 cDNA and mutant CD2 cDNA in a murine Ag-specific T cell hybridoma that responds to human HLA-DR Ag. Here we have expressed mutations at amino acid 91 and 92 of CD2 in the T cell hybridoma. The mutated CD2 molecules were functional in that pairs of anti-CD2 mAb that continued to bind were able to stimulate IL-2 production by the hybridomas. However, CD2 mutants with either the 91 or 92 amino acid substitution had lost the ability to bind to or be activated by either SRBC, which bear an LFA-3 homologue, or by murine L cells expressing human LFA-3. Unlike hybridomas expressing the wild-type CD2 molecule, there was no enhanced response to Ag stimulation. Taken together, these data suggest that the mutated CD2 molecules were no longer able to bind to, or to utilize, LFA-3 for activation. We have previously demonstrated that a mutation at amino acid 51 of CD2 results in loss of binding to LFA-3. Whether these two regions of CD2, discrete and separable by amino acid sequence, form one or more binding sites for LFA-3 remains to be determined.
CD4+ T cell response to the human acetylcholine receptor alpha subunit in myasthenia gravis. A study with synthetic peptides.
Authors: Protti M P , Manfredi A A , Straub C , Howard J F , Conti-Tronconi B M 
Published: December 2022

Abstract
The production of antinicotinic acetylcholine receptor (AcChR) antibodies in myasthenia gravis (MG) is modulated by specific Th (CD4+) lymphocytes that can recognize epitopes on the denatured AcChR alpha subunit. Thirty-two overlapping synthetic peptides corresponding to the complete sequence of human AcChR alpha subunit were used to investigate the anti-alpha subunit response of unselected lymphocytes and of CD8(+)-depleted, CD4(+)-enriched lymphocytes from the blood of nine MG patients and from four healthy controls. One subject was a newly diagnosed MG patient that was tested three times after the development of the disease. An anti-AcChR response of the CD4(+)-enriched cells was present that could be detected only after removal of the CD8+ population and that seems to be related to the clinical conditions of the patient. The high basal rate of the cell proliferation of the unselected unstimulated blood lymphocytes and the normal basal rate observed for the CD8(+)-depleted population suggested the presence of activated CD8+ cells. The study of surface markers of the T cells confirmed the existence of activated CD8+ and CD4+ cells in numbers correlated with the severity of the disease and the results of the in vitro response of the T cells. The anti-AcChR activity of the CD4+ cells in MG may be a useful marker of the activity of the disease and it seems to be influenced by activated CD8+ cells present in the patients' blood.
Molecular mimicry between a uveitopathogenic site of S-antigen and viral peptides. Induction of experimental autoimmune uveitis in Lewis rats.
Authors: Singh V K , Kalra H K , Yamaki K , Abe T , Donoso L A , Shinohara T 
Published: December 2022

Abstract
S-Antigen (S-Ag) is a well characterized 45,000 m.w. photoreceptor cell protein. When injected into susceptible animal species, including primates, it induces an experimental autoimmune uveitis, a predominantly T cell-mediated autoimmune disease of the retina and uveal tract of the eye, and of the pineal gland. In this study we found an amino acid sequence homology between a uveitopathogenic site of S-Ag, several viral proteins and one additional nonviral protein. An experimental autoimmune uveitis and pinealitis was induced in Lewis rats with these different synthetic peptides, corresponding to the amino sequence of hepatitis B virus DNA polymerase, gag-pol polyprotein of Baboon endogenous virus and gag-pol polyprotein of AKV murine leukemia virus and potato proteinase inhibitor IIa, which contain three or more consecutive amino acids identical to peptide M in S-Ag. Lymph node cells from rats immunized with either peptide M or the different synthetic peptides showed a significant degree of cross-reaction. Mononuclear cells from monkeys (Macaca fascicularis) immunized with peptide M also showed significant proliferation when incubated with either peptide M or synthetic peptides as measured by in vitro lymphocyte mitogenesis assay using [3H]TdR. Based on our findings we conclude that a viral infection may sensitize the mononuclear cells that can cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoantigenic event can take place in the absence of the infectious virus that initiated the immune response.
IL-1 and its receptor are translocated to the nucleus.
Authors: Curtis B M , Widmer M B , deRoos P , Qwarnstrom E E 
Published: December 2022

Abstract
The internalization and intracellular transport of IL-1 and its receptor were examined in the murine T cell line EL-4. For 4 h after internalization intracellular 125I-IL-1 alpha remains bound to its receptor without degradation. Electron microscope autoradiography demonstrates that internalized IL-1 accumulates in purified nuclei. The IL-1 extracted from these nuclei is still bound to receptor. As no receptors for IL-1 were detected in untreated nuclei, these results suggest IL-1 driven translocation of the cell surface IL-1R complex to the nucleus. IL-1R internalization was correlated with IL-1 signal transduction events required to induce growth factor production from several subclones of EL-4 cells. The subsequent transport of the internalized IL-1R complex to the nucleus suggests the possibility for a nuclear site for IL-1R signaling.
Leukocyte specificity and binding of human neutrophil attractant/activation protein-1.
Authors: Leonard E J , Skeel A , Yoshimura T , Noer K , Kutvirt S , Van Epps D 
Published: December 2022

Abstract
Neutrophil attractant/activation protein-1 (NAP-1) was previously shown to attract human neutrophils, but not monocytes. The purpose of this study was to determine if NAP-1 interacted with other types of blood leukocytes. In addition to its chemotactic activity for neutrophils, NAP-1 induced chemotactic responses by T lymphocytes and basophils. Chemotactic potency (10(-8) M for an optimal response) was the same for all three cell types. However, NAP-1 caused a chemotactic response in excess of random migration of 7% or 16% of basophils (depending on the medium used) and only 9% of T lymphocytes, in contrast to 30% of neutrophils. This agonist was not chemotactic for partially purified normal human eosinophils. The symmetrical histogram obtained by flow cytometry of neutrophils equilibrated at 0 degree C with fluoresceinated NAP-1 indicates that all neutrophils bound the ligand. A dose-response curve plateau, and inhibition of binding of NAP-1-FITC by unlabeled ligand are evidence for saturable binding to receptors, estimated to be 7000 per cell. Our results suggest that, for induction of an acute inflammatory response, the quantitatively significant action of NAP-1 is on neutrophils.
IL-4 potentiates the IL-2-dependent proliferation of mouse cytotoxic T cells.
Authors: Miller C L , Hooton J W , Gillis S , Paetkau V 
Published: December 2022

Abstract
In addition to the regulation of B lymphocyte growth and differentiation, the cytokine IL-4 (BSF-1) exerts effects on T lymphocytes and other bone marrow-derived lineages. We show here that recombinant mouse IL-4 synergizes with low levels of IL-2 to increase the yield of cytotoxic activity in a primary MLR, and the proliferation of both cloned IL-2-dependent CTL lines and cells obtained from a primary MLR. IL-4 did not induce the proliferation of any of several cloned CTL cell lines on its own. It also did not replace IL-2 in stimulating the growth or reactivation of quiescent, antigen-dependent CTL clones. However, IL-4 was synergistic with IL-2 after reactivation of the quiescent cells with antigen plus IL-2. Enhancement by IL-4 of the IL-2-driven proliferation of an antigen-independent line was blocked by the addition of anti-IL-4 monoclonal antibody. Although incubation of the CTL clones with IL-4 or with IL-2 plus IL-4 induced a transient increase in the expression of the mRNA encoding the 55 kDa IL-2 receptor, no change in the number or affinity of IL-2 receptors because of IL-4 was detected. This suggests that IL-4 does not potentiate the IL-2 response by altering IL-2 receptor levels. Instead, we propose that the synergistic effect of IL-4 is mediated by a different signalling mechanism from that used by IL-2.
Immunogenic peptides require an undisturbed phospholipid cell membrane environment and must be amphipathic to immobilize Ia on B cells.
Authors: Mecheri S , Dannecker G , Dennig D , Hoffmann M K 
Published: December 2022

Abstract
Ia-reactive immunogenic peptides have been shown to immobilize Ia molecules on the B cell surface and to facilitate their aggregation with specific alloantibody. We show that to immobilize Ia the peptide must be amphipathic. Polar peptides appear to bind to Ia molecules as judged by competitive inhibition, but do not immobilize the MHC molecule. This suggests the possibility that peptides establish the immobilizing membrane contact via a lipophilic group. Examining the B cell membrane lipid environment, we found that treatment of B cells with phospholipase C prevents peptide-mediated immobilization of Ia. The requirement of a lipophilic peptide portion as well as of phospholipase-sensitive membrane components for effective peptide-mediated Ia aggregation on B cell membranes suggests a role for membrane phospholipids in this process. We advance the speculation that immunodominant amphipathic peptides immobilize Ia molecules by attaching them to cell surface phospholipids which we tentatively refer to as immobilizing phospholipids.
Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody.
Authors: Mueller B M , Romerdahl C A , Gillies S D , Reisfeld R A 
Published: December 2022

Abstract
A mouse/human chimeric antibody (ch14.18) was developed that reacts with the disialoganglioside GD2 on the surface of tumor cells of neuroectodermal origin. ch14.18 has the constant regions of a human IgG1 antibody and was expressed in a murine hybridoma. This antibody was produced in tissue culture at concentrations up to 180 mg/liter of spent culture fluid. ch14.18 was characterized and compared to 14.G2a, a murine mAb against GD2 of IgG2a isotype derived from the same parental hybridoma as ch14.18. Scatchard plot analysis of data from saturation binding studies on M21 melanoma cells showed identical binding for ch14.18 and 14.G2a. Indirect immunofluorescence revealed the same staining pattern for ch14.18 and 14.G2a on different melanoma cell lines. Both antibodies were equally capable of targeting M21 xenografts in athymic nude mice. ch14.18- and 14.G2a-activated human C-mediated cytolysis of melanoma cell; however, ch14.18-mediated antibody-dependent cytotoxicity of human effector cells against melanoma cells 50- to 100-fold more efficiently than 14.G2a.