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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A method is described for stimulating proliferation in primed populations of murine T lymphocytes using antigen bound to mitomycin-C-treated spleen cells. This form of antigen presentation appears to be an active process because heat-killed spleen cells are ineffective, and because genetic similarity at the major histocompatibility complex (MHC) between the responder T cells and the presenting spleen cells is required for effective interactions. At all times examined, from day 3 to day 6 of the proliferative response, syngeneic spleen cells presented antigen better to peritoneal exudate T-lymphocyte-enriched cells (PETLES) than semisyngeneic F(1) spleen cells, which in turn could present antigen better than totally allogeneic spleen cells. Spleen cell mixing experiments demonstrated that these genetic restrictions were not the result of suppression by the ongoing mixed lymphocyte reactions (MLR) in the allogeneic and F(1) cases. Furthermore, incompatibility at the Mls locus generated a strong MLR but failed to prevent antigen presentation if the spleen cells and PETLES were compatible. Genetic mapping studies demonstrated that compatibility at only the I-A subregion of the MHC was sufficient for effective presentation of the antigen, dinitrophenylated ovalbumin. Compatibility at only the K region, or the K and D regions was not sufficient. These results support the concept that functional activation of primed, proliferating T lymphocytes requires the participation of gene products coded for by the I region of the MHC. This conclusion is consistent with a growing body of evidence which suggests that most T cells recognize antigen in association with MHC gene products.
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PMID:Antigen presentation in the murine T-lymphocyte proliferative response. I. Requirement for genetic identity at the major histocompatibility complex. 7 Apr 97

Murine and human beta 2-microglobulin (beta 2m) bind to various types of mouse cells. The binding is saturable and displays a single association constant of about 1 x 10(9) liter/mol. The binding of beta 2m to splenocytes was not affected by a variety of metabolic inhibitors but was temperature-dependent. It is suggested that the beta 2m "receptor" exhibits a temperature-dependent conformational change since the "receptor", whether integrated into the membrane or solubilized by the detergent Triton X-100, binds beta 2m poorly at low temperatures. Spleen T and B lymphocytes display more binding sites than thymocytes, kidney, liver and brain cells. The relative amounts of the beta 2m-binding "receptor" on these cell types are strongly correlated to the relative amounts of H-2 antigens. This correlation is also obvious for the teratocarcinoma cell line F9, which lacks both beta 2m "receptor" and H-2 antigens, but spermatozoa, which express very small amounts of H-2 antigens, have an appreciable amount of the beta 2m "receptor". The latter observation, together with the fact that alloantisera directed against H-2 K and D antigens do not measurably affect the binding of beta 2m to the "receptor", may argue against the notion that the beta 2m "receptor" represents H-2 antigens which have lost their endogenous beta 2m. Normal mouse serum contains a component which inhibits the binding of beta 2m to splenocytes. It is likely that this serum protein is identical to a newly discovered H-2 antigen-like glycoprotein. The beta 2m "receptor" appears to be under the control of the major histocompatibility complex as splenocytes of the H-2f haplotype bind considerably more beta 2m than splenocytes of other haplotypes.
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PMID:Demonstration of a murine cell surface component with affinity for exogenous beta 2-microglobulin. 9 8

Spleen cells from a LEW.AVN rat immunized with cells from an MNR rat were fused with mouse myeloma cells to produce hybrid cell lines. One of these hybridomas produced a monoclonal antibody that was cytotoxic for bone marrow-derived (B) but not thymus-derived (T) cells. The antigen defined by this antibody is determined by a gene linked to the major histocompatibility complex (MHC). The antigen is also present on B cells of most mouse strains and is determined by an MHC-linked gene in this species as well. In both rats and mice, the gene determining the antigen maps within the immune response region of the MHC. All human B-cell lines, but not T-cell lines, and B but not T cells of all human donors tested so far are also positive for this antigen. Among human-mouse somatic cell lines that have lost various human chromosomes, this B-cell antigen is present on all lines that are positive for HLA antigen but is absent from all lines that have lost HLA.
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PMID:Monoclonal antibody directed to a B-cell antigen present in rats, mice, and humans. 31 63

Dendritic cells (DCs; 1) have been purified from mouse spleen in good yield. Spleen cell suspensions were floated on dense bovine plasma albumin (BPA) columns, and the low density fraction was adhered to glass (2). The adherent cells consisted of DCs and immature macrophages most of which eluted in a viable state from the culture dish after overnight incubation. The macrophages were then removed by selective rosetting with opsonized erythrocytes and recentrifugation on dense BPA. This protocol resulted in a purified DC fraction, containing 1--3 X 10(5) DCs/spleen, which was homogeneous and distinctive in its properties. All cells exhibited the phase contrast and transmission electron microscopy (EM) cytologic features that were previously described for freshly isolated adherent DCs. By scanning EM, most purified DCs exhibited a remarkable array of bulbous protrusions of varying length and shape, unlike any other lymphoid cell. All DCs expressed surface Ia and other major histocompatibility complex (MHC)-linked alloantigens. DCs, however, lacked surface Ig and T-cell antigens, and did not bind or interiorize opsonized erythrocytes. Purified DCs have been maintined in vitro for 3 days. Recovery of cultured purified cells was 70% or more of starting cell numbers. When [3H]uridine-tagged DCs were mixed with nonlabeled heterogeneous spleen cells, 70--80% of the labeled DCs were recovered as viable cells 2--3 days later. Purified DCs did not readhere to tissue culture surfaces and did not proliferate, even when cultured with mitogenic doses of concanavalin A and lipopolysaccharide. Finally, DCs did not change their cytologic or surface properties after 3 days of culture. These observations extend the evidence that DCs are a novel cell type and provide useful properties and techniques for their further study.
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PMID:Identification of a novel cell type in peripheral lymphoid organs of mice. V. Purification of spleen dendritic cells, new surface markers, and maintenance in vitro. 76 93

Plasmid vector sequences were retained (vector+), or removed (vector-) from hybrid major histocompatibility complex gene constructs prior to microinjection of fertilized ova for the production of transgenic mice. In transgenic mice containing integrated vector+ gene constructs, low levels of class II cell surface determinants were detected on splenocytes from only two out of six independent lines. Class II membrane determinants were not detectable on splenocytes from the remaining four vector+ transgenic lines. Expression of transgene products did not correlate with transgene copy number which ranged from 1-10 copies. Low levels of mRNA transcripts were detected in thymic mRNA from vector+ lines. In contrast, high levels of thymic and splenic mRNA transcripts were detected in offspring from all four vector- transgenic lines. Spleen cells from the vector- transgenic animals also expressed high levels of the hybrid major histocompatibility complex transgene products. These results implicate plasmid vector sequences in the inhibition of expression of the hybrid class II-class I major histocompatibility complex genes in transgenic mice. This putative inhibition of transgene expression presumably occurs at the level of gene transcription.
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PMID:Impaired expression of chimaeric major histocompatibility complex transgenes associated with plasmid sequences. 130 Dec 11

Changes in the antigenicity of major histocompatibility complex (MHC) class I molecules resulting from the association of bovine beta 2-microglobulin (beta 2-m) with mouse class I heavy chains were investigated. Mice (H-2b) were immunized with syngeneic Concanavalin A (Con A) blasts induced in the presence of fetal calf serum (FCS) in conditions allowing exchange between mouse and bovine beta 2-microglobulin (beta 2-m). Spleen cells from hyperimmunized mice were fused with myeloma cells and two monoclonal antibodies which required for their reactivity the presence of FCS have been further studied. One of them (CAB 297) recognized a determinant of bovine beta 2-m which is present on free molecules in solution as well as when they are associated with either mouse or bovine class I heavy chains. In contrast, the second monoclonal antibody (CBB 70) did not react with free bovine beta 2-m molecules, nor with beta 2-m associated with bovine class I heavy chains. It did react with cells of some H-2 haplotypes (b, f, p and r) but only when their class I heavy chains are associated with bovine or with human beta 2-m. Therefore, expression of the CBB 70 defined antigenic determinant requires both xenogeneic beta 2-m and class I heavy chain of a given H-2 molecule. In order to precisely localize the antigenic determinant defined by this monoclonal antibody and therefore the region altered by the association of class I heavy chain with xenogeneic beta 2-m, we made use of exon shuffled class I molecules. The results indicate that changes induced by the association of bovine beta 2-m with H-2 class I heavy chain affect the conformation of the alpha 2 domain. These studies illustrate that MHC class I molecules exhibit a considerable conformational flexibility which could influence their ability to bind and present various peptides to the T-cell receptor.
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PMID:Localization of the conformational alteration of MHC molecules induced by the association of mouse class I heavy chain with a xenogeneic beta 2-microglobulin. 137 66

We have investigated the ability of various antigen-presenting cell (APC) types to induce primary anti-viral cytotoxic T lymphocyte (CTL) responses by single in vitro stimulation. Of these APC types, only dendritic cells (DC) and RMA-S lymphoma cells could induce primary CTL responses, but by divergent mechanisms. DC were capable of generating primary virus-specific CTL, either by presenting viral peptide or processed infectious virus. In contrast, RMA-S cells could not present endogenous antigen, e.g. after virus infection, but this cell line very efficiently presented exogenous viral peptides to induce primary virus-specific CTL in vitro. Spleen cells, lipopolysaccharide-induced B cell blasts or the non-mutated RMA cells did not have the ability to trigger unprimed T cells by single in vitro stimulation. We have investigated several characteristics important for primary CTL response induction by DC and RMA-S cells (summarized in Fig. 6). Primary CTL response induction by DC or RMA-S cells was blocked by anti-LFA-1 or anti-CD8 monoclonal antibodies (mAb). DC rapidly aggregated with unprimed T cells, which was independent of LFA-1 and CD8 molecules. RMA-S cells did not form conjugates with unprimed T cells. Despite their abundant major histocompatibility complex (MHC) class I cell-surface expression, DC did not bind much exogenously added viral peptide. In contrast, the MHC class I molecules on RMA-S cells bound a large quantity of exogenously administered peptide. Powerful adhesion by DC and high expression of relevant MHC/peptide complexes on RMA-S cells are important features in the initial contact with unprimed T lymphocytes. In a later stage of contact, both DC and RMA-S cells activate LFA-1 (and CD8) molecules at the T cell surface to strengthen and maintain the contact between T cell and APC.
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PMID:Mechanisms of induction of primary virus-specific cytotoxic T lymphocyte responses. 142 25

Cytotoxic T lymphocyte (CTL) responses to most antigens are generated by in vivo priming and secondary stimulation with antigen in vitro. The present studies were designed to determine whether that strategy could be used to stimulate development of CTL against brain tumors. Rats were primed with one of two tumors, RT2, an astrocytoma, or 9L, a gliosarcoma, and Corynebacterium parvum. Spleen cells from primed rats were stimulated with tumor cells and interleukin-2 in vitro to generate CTL. CTL generated against RT2 killed RT2 and 9L, but not allogeneic or histopathologically unrelated tumor cells, suggesting that the killing was brain tumor-specific and major histocompatibility complex gene product-restricted. Similar results were obtained with rats primed and secondarily stimulated with 9L. Specific cytotoxic cells only developed when syngeneic brain tumor cells were used for both priming and secondary stimulation. The cytotoxic cell populations were composed of OX-19+ T cells with a mixed CD4/CD8 phenotype. Controls consisting of spleen cells from unprimed or primed rats tested before culture exhibited low levels of cytotoxicity against brain tumor targets. Culturing unprimed or primed cells with interleukin-2 alone stimulated cell proliferation, but the cells that grew out exhibited only low levels of cytotoxicity for brain tumor cells. Cell populations exhibited consistent cytotoxicity against natural killer cell targets. None of the cell populations killed lymphokine-activated killer cell targets. The results demonstrated that brain tumor-specific CTL could be produced by priming in vivo followed by secondary stimulation with brain tumor cells in vitro. The results further demonstrated that RT2 and 9L share antigens that both induce and serve as target structures for specific cytotoxic cells.
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PMID:Generation of cytotoxic immune responses against a rat glioma by in vivo priming and secondary in vitro stimulation with tumor cells. 158 47

Cytotoxic T lymphocytes (CTL) play an important role in recovery from a number of viral infections. They are also implicated in virus-induced immunopathology as best demonstrated in lymphocytic choriomeningitis virus (LCMV) infection of adult immunocompetent mice. In the present study, the structure of the T-cell receptor (TCR) in LCMV-specific CTL in C57BL/6 (B6) mice was investigated. Spleen T cells obtained from LCMV-infected mice were cultured in vitro with virus-infected stimulator cells and then stained with anti-TCR V beta antibodies. A skewing of V beta usage was noticeable in T cells enriched for their reactivity to LCMV, suggesting that particular V segments are important for the recognition of LCMV T-cell epitopes in B6 mice. To gain more detailed information on the structure of the TCR specific for LCMV epitopes, we studied CTL clones. It has been shown that approximately 90% of LCMV-reactive CTL clones generated in H-2b mice are specific for a short peptide fragment of the LCMV glycoprotein, residues 278 to 286, recognized in the context of the class I major histocompatibility complex molecule, Db. Four CTL clones possessing the specificity were randomly selected from a collection of clones, and their TCR genes were isolated by cDNA cloning or by the anchored polymerase chain reaction. All four clones were found to use V alpha gene segments belonging to the V alpha 4 subfamily. By RNA blot analysis, two more clones with the same specificity were also shown to express the V alpha 4 mRNA. In contrast, three different V beta gene segments were used among the four clones examined. J beta 2.1 was used by three of the clones. Although amino acid sequences in the V(D)J junctional regions were dissimilar, aspartic acid was found in the V alpha J alpha and/or V beta D beta J beta junctions of all four of these clones, suggesting that this residue is involved in binding the LCMV fragment. Restricted usage of V alpha and possibly J beta segments in the CTL response to a major T-cell epitope of LCMV raises the possibility that immunopathology in LCMV infection can be treated with antibodies directed against such TCR segments. Thus, similar analysis of the TCR in other virus infections is warranted and may lead to therapeutic strategies for immunopathology due to virus infections.
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PMID:Restricted V-segment usage in T-cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus. 170 Aug 30

Rats were injected intraperitoneally from birth on with a mouse monoclonal antibody (R73) to a constant determinant of the rat T cell receptor (TcR)2. Throughout the observation period (6 months), TcR2+ cells in peripheral lymphoid organs and blood were absent in treated animals with the exception of few (less than 10%) cells with a tenfold reduced TcR2 density; peripheral TcR2-CD3+ cells, i.e. most likely TcR1+ T cells, were increased in frequency. Among thymocyte subpopulations, only those expressing the TcR2 at a high level were reduced in number. The lack of a visible effect on immature thymocytes may, however, be due to the fact that despite high serum levels, thymic R73 determinants were incompletely saturated. Spleen and lymph node cells from TcR2-suppressed rats were completely unresponsive in mixed lymphocyte reaction (two fully allogeneic haplotypes tested) even in the presence of interleukin 2. Reactivity to the T cell mitogen concanavalin A was, in contrast, only partially reduced. Since rat TcR1 cells are activated by concanavalin A, these results suggest that the TcR1 cells present in TcR2-suppressed rats are functional, but do not respond to foreign major histocompatibility complex antigens at a high frequency, a finding of possible importance for immunosuppression with anti-TcR2 monoclonal antibody in human allografting. Neonatally TcR2-suppressed rats were unable to respond to the strong T-dependent antigen keyhole limpet hemocyanin administered intraperitoneally in alum with B. pertussis. Thus, in the absence of peripheral TcR2 cells, the numerically expanded TcR1 T cells are not capable of providing help for B lymphocytes.
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PMID:The neonatally T cell receptor 2-suppressed rat: lymphocyte subset composition and immune reactivity. 170 19


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