Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present work, we tested in SCID and Balb/c mice the activity of T hybridoma transfected with T cell receptor (TCR) alpha/beta chain genes. A T cell hybridoma denoted D011107 was used as recipient for transfection of cytotoxic KB5C20 TCR alpha/beta heterodimer genes by protoplast fusion or electroporation. After transfection, the parental D011107 T cell line reexpressed CD5 and CD4 surface molecules. In vitro, we noted strong proliferation and unusual cytotoxic reactivities against H-2k target cells although the transfected cell line does not express the CD8 molecule. The fate of parental and transfected cells was examined in severe combined immunodeficient (SCID) and Balb/c mice at Day 16 after intravenous injection. Cells from bone marrow, thymus, and spleen tissues were analyzed by immunofluorescence. The transfected T cell hybridoma was CD3+ Desire 1+ CD4+ Thy1.2. The SCID mice grafted with the transfected T cell hybridoma presented a high percentage of CD3+ (15%), CD4+ (27%), Thy1.2+ (27.52%), and Desire 1+ (8.74%) cells in the spleen. The percentages of CD3+ (6.2%) and Thy1.2+ (5.06%) cells in the spleen from SCID mice grafted with parental T cell D011107 and from untreated SCID were similar and lower (CD3+, 3.52%; Thy1.2+, 4.34%). It seems that transfected T cells hybridoma grafted in the SCID mice induce significant expression of CD4+ Thy1.2+ Desire 1- cells (17%) in the spleen. These results indicate that transfected T cells graft may allow T cell differentiation. In Balb/c mice, the percentage of different T cell subsets in bone marrow, thymus, or spleen cells in mice injected with transfected T cells was similar to that in untreated mice. We did not observe any cytotoxic or significant allogeneic proliferation in vitro.
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PMID:T hybridoma alpha/beta gene transfected in a murine T cell hybridoma: role of CD4 molecule in vitro and in vivo--engraftment in SCID mice induces T cell maturation. 135 32

The induction of antigen-specific tolerance in mice by conjugates of ovalbumin (OVA) and monomethoxypolyethylene glycol (mPEG) previously had been shown to be associated with the generation of antigen-specific suppressor T (Ts) cells. For the elucidation of the nature of these Ts cells, five nonhybridized OVA-specific Ts cell clones were generated from the spleen cells of a BDF1 mouse which had been immunosuppressed by the tolerogenic conjugate, OVA(mPEG)12. The cloned Ts cells were maintained in vitro by periodic stimulation with OVA and feeder cells and were able to suppress the in vitro antibody production in an OVA-specific and MHC class I (H-2Kd or H-2Dd)-restricted manner. All these Ts cell clones were shown to be Thy1.2+, CD4-, CD5-, CD8+, and to express CD3 and the alpha beta heterodimer of the T cell receptor. The cell-free extracts of these cells contained soluble suppressor factors which could mimic in vitro the suppressive activity of the intact cells. In contrast to cytotoxic T lymphocytes (CTL), none of the cloned Ts cells were endowed with cytolytic activity as revealed in the perforin-mediated microhemolysis and in the 18-hr51Cr release assays. These results demonstrate that (i) OVA-specific Ts cell clones can be generated from mice pretreated with OVA(mPEG)12 by employing conventional T cell culture techniques, and (ii) these Ts cells are functionally different from conventional CD8+ CTL.
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PMID:Characterization of suppressor T cell clones derived from a mouse tolerized with conjugates of ovalbumin and monomethoxypolyethylene glycol. 153 37

A detailed phenotypic analysis of intraepithelial lymphocytes (IEL) of the small intestine was performed using multicolor fluorescence flow cytometry. CD4+8+ IEL (double positives; DP) could be detected in significant numbers in preparations from several mouse strains. DP IEL expressed Tcr alpha, beta and Thy1. Comparison of Tcr alpha, beta levels of thymocytes and IEL revealed that whereas the majority of DP thymocytes expressed low Tcr levels, DP IEL expressed high, mature T cell levels of Tcr. In addition, DP IEL were generally Ly3- (CD8 beta), unlike their thymic counterparts, which are Ly3+. Ly3 was not present on Tcr gamma, delta IEL, whereas CD4-8+ Tcr alpha, beta IEL contained Ly3- and Ly3+ subsets. The Ly3- population in either Tcr-bearing subset could be further subdivided by Thy1 expression. Ly1 (CD5) expression was also examined, and none of the Tcr gamma, delta IEL were Ly1+. Based on Thy1, Ly3, and Ly1 expression, four CD4-8+ Tcr alpha, beta IEL subsets were detected. The results indicate the cellular complexity of the IEL compartment rivals that found in the thymus. These findings are discussed in light of recent data suggesting an extrathymic origin of some IEL.
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PMID:Phenotypic complexity of intraepithelial lymphocytes of the small intestine. 171 78

Recent results of studies employing tolerogenic monomethoxypolyethylene glycol (mPEG) conjugates of antigens are briefly reviewed. Administration of antigen (mPEG)n conjugates into mice induced antigen-specific suppressor T (Ts) cells, from which a suppressor factor (TsF) was extracted. These Ts cells were cloned and shown to be Thy1.2+, CD3+, CD4-, CD5-, CD8+ and to express the alpha beta heterodimer of conventional T cell receptors (TCR). The TsF of a clone of OVA-specific Ts cells shared the epitopes of the alpha and beta chains of TCR, whereas the TsF of T cells of an HIgG-specific clone shared only the epitope of the alpha chains of TCR; OVA and HIgG represent ovalbumin and human monoclonal (myeloma) IgG. These studies have provided evidence for the phenomenon of "linked immunological suppression" which may be summarized by the statement "Ts cells specific for an epitope of a given antigen, AgA, suppress the antibody response to an unrelated antigen, AgB, only if the latter is presented in the form of a covalent adduct, AgA-AgB, to the immune system of the animal pretolerized with AgA (mPEG)n, but not if AgB is presented as a mixture with AgA.
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PMID:Suppressor T cells induced in vivo by tolerogenic conjugates of a given antigen and monomethoxypolyethylene glycol downregulate antibody formation also to a second antigen, if the latter is presented as a covalent adduct with the former. 183 92

Graft-versus-host disease (GVHD) was induced across the murine major histocompatibility complex by injecting C57BL/6 (H-2b) bone marrow and splenocytes into lethally irradiated B10.BR (H-2k) murine recipients. An immunotoxin (IT) composed of a pan T-cell monoclonal antibody called anti-Ly1 (the murine homologue to human anti-CD5) was conjugated to ricin toxin A chain (anti-Ly1-RTA) and used to treat recipient mice. In vitro, IT was as active as free RTA, bound selectively, and inhibited T-cell proliferation even in the absence of potentiators. Mice administered anti-Ly1-RTA in vivo during ongoing GVHD, at a dose of 10 micrograms/d for 5 days, showed lower numbers of splenic Thy1.2+ T cells and significantly improved survival as compared with mice given phosphate-buffered saline (PBS) or irrelevant control RTA IT. Protection was transient because GVHD and weight loss occurred when injections ceased. Survival could not be enhanced by crosslinking RTA30, a low oligosaccharide-containing fraction of purified RTA. Treatment with anti-Ly1-RTA caused a significant elevation in neutrophils, and higher doses were associated with mild hepatotoxicity. In contrast, infusion of identical doses and schedules of another pan T-cell immunotoxin, anti-Thy1.2-RTA, caused a significant decrease in lymphocytes, but not neutrophils; a precipitous increase in weight; a decrease in total plasma protein (TPP); and an increase in pleural and peritoneal effusions reminiscent of vascular leak syndrome (VLS). Although the toxic effects of anti-Thy1.2-RTA were too severe to show a survival advantage in a GVHD model, histopathologic studies showed a definite anti-GVHD effect. The most significant decline in GVHD as compared with the PBS-treated controls was observed in skin, and to a lesser extent, in liver and lung. To investigate the cause of IT toxicity, anti-Thy1.2-RTA was administered intraperitoneally to lethally irradiated B10.BR (H-2k) recipients of syngeneic bone marrow. These recipients showed the same weight gain, hypoproteinuria, and VLS observed in the GVHD model. Death occurred at higher anti-Thy1.2-RTA doses (30 or 50 micrograms/daily injections administered days 8 through 12 posttransplant). Anti-Thy1.2-RTA had a negligible effect on renal function, but histologic studies showed patchy dropout of the renal tubules. Treatment resulted in pulmonary vascular congestion, but there was no pathologic evidence of liver, brain, or colon toxicity. Weight gain was enhanced by irradiation because nonirradiated normal mice did not undergo such a precipitous weight increase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Toxicity and efficacy of anti-T-cell ricin toxin A chain immunotoxins in a murine model of established graft-versus-host disease induced across the major histocompatibility barrier. 198 94

To examine whether intracellular free calcium ([Ca2+]i) signals are reduced in murine T-lymphocyte subsets in aging, we used a flow cytometric assay with the dye indo-I and simultaneous immunofluorescence. Calcium response was reduced in both CD4+ and CD8+ subsets, after stimulation with concanavalin A or anti-CD3 monoclonal antibody over a broad range of concentrations. Experiments carried out in the presence of EGTA indicate that both calcium mobilization from internal stores and extracellular calcium influx were reduced. The reduced overall response was in part due to a decreased number of responding cells in aged animals. In contrast, the [Ca2+]i response produced by the crosslinking of Thy1 and Ly1 (CD5) surface molecules did not show significant differences between young and old mice, indicating that some signaling mechanisms are intact in aged animals. These data also suggest that there are substantial differences between humans and mice in age-related changes in signal transduction.
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PMID:Aging-related deficiency in intracellular calcium response to anti-CD3 or concanavalin A in murine T-cell subsets. 213 84

Binding of cognate Radiation leukemia virus (RadLV) by the C6VL/1 thymoma involves a subset of TCR molecules in association with CD4 molecules expressed by that cell line. A CD4- variant of C6VL/1 has now been isolated which also has RadLV binding capacity. Stable expression of the TCR, class I, and CD5 molecules but not Thy1.2 and CD4 molecules has been demonstrated, and the C6VL/1 origin of this cell has been confirmed by Southern blot analysis using probes specific for the TCR beta chain gene. This cell line has maintained binding capacity for RadLV/C6VL prepared as an immunoabsorbent matrix, but unlike the parent C6VL/1 cell line, binds significantly less well to the related RadLV/VL3 isolate. Binding of the variant cell line to RadLV/C6VL can be completely inhibited by anti-clonotypic antibody to the TCR but only weakly by anti-H-2Kb antibody used at the same concentration. These data suggest that the TCR on C6VL/1 can interact with RadLV in the absence of any co-receptor function of CD4 and implicates the TCR as a sufficient receptor for retrovirus.
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PMID:Unique role for the T cell receptor in retrovirus binding by the C6VL thymoma. 217 45

Pulmonary intraparenchymal leukocytes were purified from normal mice. By flow cytometry, 20-30% of the lymphocytes were positive for the expression of Mac1, a cell-surface antigen largely restricted to macrophages, neutrophils and natural killer (NK) cells. Sorted Mac1+ lung lymphocytes were large and had abundant cytoplasm with few azurophilic granules. Because Mac1+ lymphocytes did not contain any asiallo GM1+ cells, they are not likely to be NK cells. By a two-color flow cytometric analysis, Mac1+ lymphocytes were demonstrated to be TCR-alpha beta intermediate+, TCR-gamma delta-, CD3intermediate+, CD4-, CD8-, Thy1-, CD5-, and B220-. These Mac1+ alpha beta T cells were not found in other organs such as spleen, thymus, liver, bone marrow and intestine of mice uninfected and infected with Mycobacterium bovis BCG. There was a considerable population of this unusual subset of alpha beta T cells in the lungs of congenitally athymic nude mice. In the Mac1+ alpha beta T-cell population, the proportions of V beta 8+ T cells and of forbidden T-cell clones expressing V beta 6 TCR were not much different from that in the conventional T-cell population. These results indicated that extrathymically developed alpha beta T cells reside in considerable proportions in the lung and that Mac1 clearly discriminates these cells from conventional ones. Interestingly, the proportion of these cells increased in the lungs of mice infected with M. bovis BCG, which raises a possibility that these cells may play some role in the host defense against mycobacterial infection.
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PMID:Mac1 discriminates unusual CD4-CD8- double-negative T cells bearing alpha beta antigen receptor from conventional ones with either CD4 or CD8 in murine lung. 759 Sep 10

Up to 90% of CD8+ intraepithelial lymphocytes (IEL) of the murine large intestine (LI) belong to the alpha/beta T cell lineage and consist of two subsets. One subset expresses both alpha and beta subunits of the CD8 coreceptor, and is uniformly Thy1+, CD5+, B220-, CD2+, CD28+. The CD8 alpha+beta+ LI-IEL exclude self-reacting V beta structures, and readily proliferate in vivo in response to T cell receptor-mediated stimuli. The CD8 alpha+beta- subset of TCR-alpha/beta+ LI-IEL is Thy1-/+, CD5-, B220+, CD2+/-, and CD28-. It contains cells with potentially self-reacting V beta s and is responsive in vivo to high doses of anti-TCR-alpha/beta monoclonal antibody (mAb), but not to bacterial superantigens. Both subsets are abundant in LI-IEL of old nude mice, and CD8 alpha+beta+ LI-IEL in nude mice undergo the same V beta deletions as in euthymic mice of the same background. Both subsets express the intestinal T cell-specific integrin alpha M290 beta 7, known to be a homing receptor for IEL. Unusually high proportions of CD69+ cells within both subsets indicate chronic activation. The proportions of CD69+ and alpha M290 beta 7+ cells within the CD8 alpha+beta+ subset increase with age, probably due to constant antigenic challenge. We propose that CD8 alpha+beta+ and CD8 alpha+beta- subsets of LI-IEL permanently reside in LI and represent a lineage different from spleen and lymph node CD8+ T cells. The CD8 alpha+beta+ undergoes negative selection, and is responsive to TCR-mediated stimuli. The CD8 alpha+beta- subset of LI-IEL is a subject of distinct selection mechanisms, and has low responsiveness to TCR-mediated stimuli.
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PMID:Heterogeneity and biased T cell receptor alpha/beta repertoire of mucosal CD8+ cells from murine large intestine: implications for functional state. 804 26

Murine uterine T cells were analysed on the basis of surface phenotype expression from birth to adulthood. T cells were rare in the uterus from birth until 2 weeks of age. In genetically immunocompetent mice, mature T cells expressing either TCR alpha/beta or TCR gamma/delta were first present as a major cell population at 3 weeks of age. The ratio of TCR alpha/beta to TCR gamma/delta was 1:1 at 3 weeks of age and this ratio did not change during sexual maturation. Almost all uterine T cells were CD8+ and the majority of these cells expressed CD8 alpha/beta rather than CD8 alpha/alpha. Cells expressing Thy1.2 were less frequent than cells expressing CD3 while cells expressing CD5 were rare. No major changes in T cell subsets occurred at puberty. Further, the microbial flora of the mice did not alter the time of appearance, frequency or subset distribution of uterine TCR+ cells. In the uteri of immunodeficient mice of genotype scid/scid TCR+ cells were found in low numbers and the initial appearance of TCR+ cells was delayed until 5 weeks of age.
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PMID:An immunohistologic analysis of murine uterine T cells between birth and puberty. 835 Feb 98


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