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

Subcutaneous implantation of DBA/2-derived L5178Y cells into DBA/2 mice followed 10 d later by nodule excision protected 100% of mice from the rapid outgrowth of an intraperitoneal challenge of L5178Y cells given 7 d postexcision. Challenged mice remained clinically normal for 48--250 d before onset of an ultimately fatal tumor outgrowth. The numbers of L5178Y cells in the peritoneal cavity increased logarithmically for 4 d after challenge and then declined to low but detectable levels which persisted throughout the clinically normal period. Cells active in 18-h in vitro cytolytic assays against 51Cr-labeled L5178Y target cells were found in the peritoneal cavity. The effector cells were determined to be Thy1.2 positive. Their activity was tumor specific and reached peak levels 4 d after tumor challenge and then gradually declined to undectable levels during the following 70 d. Tumor emergence occurred most frequently during the period when CMC activity was no longer demonstrable in the remaining clinically normal mice. A transient peak of low level cytophilic antitumor antibody was detected about 30 d after tumor cell challenge. The temporal associations between the numbers of tumor cells and the levels of cell-mediated lysis against L5178Y cells indicate the importance of the cell-mediated cytolysis response in limiting initial tumor outgrowth and suggest its role as one of the factors responsible for long-term tumor suppression during tumor dormancy.
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PMID:The tumor dormant state. Quantitation of L5178Y cells and host immune responses during the establishment and course of dormancy in syngeneic DBA/2 mice. 31 15

The effect of a muramyl dipeptide derivative (B30-MDP) on the augmentation of antitumour immunity against highly metastatic L5178Y-ML25 mouse lymphoma cells was examined in CDF1 (Balb/c x DBA/2) mice. Mice immunized with a mixture of X-irradiated tumour cells (10(3)) and B30-MDP (100 micrograms) on 7 days prior to challenge by viable tumour cells displayed a significant decrease in metastasis towards the target organs, liver and spleen, compared with that of untreated mice. Immunization of mice with the mixture on day 5 or 7 after tumour challenge, when the level of glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in sera of mice inoculated with viable tumour cells was observed to be normal, caused less metastasis than immunization with X-irradiated tumour cells alone. Sensitization with X-irradiated tumour cells admixed with B30-MDP induced almost two times higher cytotoxicity of spleen cells against L5178Y-ML25 lymphoma cells than sensitization with X-irradiated tumour cells without B30-MDP. In contrast, cytotoxic activity of spleen cells against another target, L1210 lymphoma cells derived from BDF1 mice, was not observed by immunization with X-irradiated L5178Y-ML25 cells with or without B30-MDP. Specific lysis by splenic cells of the immunized mice against L5178Y-ML25 cells decreased to the normal level when T cells were deleted from the immunized spleen cells by the treatment of rabbit anti-mouse Thy1.2 antibody and rabbit complement. These results indicate that B30-MDP is able to augment a specific tumour immunity due to the enhancement of cytotoxicity mediated by T lymphocytes, and is useful as an immunopotentiating agent for active immunization of inactivated tumour cells.
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PMID:B30-MDP, a synthetic muramyl dipeptide derivative for tumour vaccination to enhance antitumour immunity and antimetastatic effect in mice. 144 33

We have investigated the immunosuppressive effects of a synthetic retinoid, Ro23-6457, on the in vivo development of cellular alloimmunity. We initially observed that treatment of C57B1/6 mice with 10 mg/kg/day Ro23-6457 drug could prolong the survival of DBA/2 cardiac allografts, thus verifying its immunosuppressive potential in murine experimental models. We next used the sponge matrix model of allograft rejection and limiting dilution analysis (LDA) of cytotoxic T lymphocyte (CTL) frequency to dissect this phenomenon further. In this experimental system we observed the following effects of Ro23-6457: (1) dose-dependent decrease in the number of LDA-detectable, donor-reactive CTL accumulating in sponge matrix allografts; (2) failure to interfere with in vitro assays of cellular alloimmunity, including LDA; and (3) antigen non-specific depression of LDA-detectable CTL in lymph nodes, spleen and especially in peripheral blood. For peripheral blood CTL, the drug eliminated LDA-detectable CTL, an effect that was reversible and could not be attributed to the activation of suppressor cells. Since Ro23-6457 has little effect on the number of peripheral blood Thy1.2+ cells, it appears that this drug does not physically eliminate CTL, but makes them temporarily hyporesponsive to antigen stimulation, and thus undetectable in functional assays like LDA.
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PMID:Analysis of retinoid-mediated immunosuppression in vivo. Effects of Ro23-6457 on cellular alloimmune responses. 179 Nov 42

Proliferation of islet-associated leukocytes occurred when isolated islets from 20 week-old female Non-obese Diabetic (NOD) mice were cultured with 10 U/ml recombinant interleukin-2 (rIL-2) for 7 days. Co-culture of these lymphocytes with freshly-isolated islets from 6-8 week-old NOD donors in the presence of 1 U/ml rIL-2 produced islet structural deformation within 24 h and islet cytolysis within 48 h. Three lines of evidence suggest that leukocytes were cytotoxic T lymphocytes (CTL) specific for islet cells. First, these proliferating cells adhered to NOD islets at 6 h and specifically killed islets after 48 h of culture, but the cytoadherence of these cells to the other organs including thyroid, pancreatic exocrine glands and liver from NOD mice could not be observed and the shape of tissue clumps hardly deformed after culture for 48 h. The accumulated insulin release from NOD islets to the medium after 6 h of culture was significantly increased in the presence of islet-derived cells compared with the insulin release in the absence of cells. On the contrary, lactic dehydrogenase activity released from liver and amylase activity from pancreatic exocrine glands showed on difference between with and without these cells for 6h of culture. Second, a flow cytometric analysis showed that these cells consisted of 96%Thy1.2, 70%Lyt2, and 8%L3T4-positive cells. After treatment with monoclonal anti-Thy1.2 or Lyt2 antibody and complement, these cells lost their activity to destroy NOD islets. However, these cells still had a full killing activity after the depletion of L3T4-positive cells. Third, islets of NOD (H-2 genotype KdDb), B10.GD (H-2KdDb), BALB/cA (H-2d), and DBA/2N (H-2d) were susceptible to destructive activity of these cells, whereas islets of NON (H-2b), C57BL/6N (H-2b), C57BL/10J (H-2b), and C3H/He (H-2k) mice remained intact. Furthermore, anti-Kd monoclonal antibody could prevent islet-specific cytolysis of these cells. These results suggest that CTL expressing Thy1.2 and Lyt2 phenotypes appear to recognize islet cell antigen with restriction of major histocompatibility complex (MHC) class H-2Kd and then destroy pancreatic beta cells in NOD mice.
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PMID:[Studies on the pathogenesis of type I diabetes mellitus--destruction of pancreatic beta cells by cytotoxic T lymphocytes in nonobese diabetic mice]. 218 54

In these studies, the role of T helper and T cytotoxic cells in generating intestinal graft-vs.-host disease (GVHD) was examined. Treatment of C57BL/6J (B6) splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes natural killer cells, cytotoxic T lymphocyte (CTL) precursors, and the capacity to cause lethal GVHD in irradiated B6xDBA/2 F1 (B6D2F1) mice while preserving T helper cell function. Neither control nor Leu-Leu-OMe-treated DBA/2 donor spleen and bone marrow cells were found to induce lethal GVHD in B6D2F1 recipients. However, extensive colonic GVHD developed in B6D2F1 recipients of DBA/2 bone marrow and spleen cells. Enteropathic GVHD in DBA/2----B6D2F1 mice was reduced in severity after anti-L3T4 + C treatment of donor cells, and was eliminated by anti-Thy1.2 + C or the combination of anti-L3T4 and anti-Lyt2 + C treatment of the donor cell inoculum. However, neither anti-Lyt2 + C, Leu-Leu-OMe, nor anti-Lyt2 + C and Leu-Leu-OMe treatment of donor cells significantly decreased severity of gut GVHD. Leu-Leu-OMe treatment of DBA/2 or B6 SpC was comparably effective in preventing in vitro or in vivo generation of B6D2F1-specific CTL. These findings, therefore, demonstrate that histologically severe enteropathic GVHD does not require participation of CTL and is not always associated with high mortality rates.
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PMID:Intestinal graft-versus-host disease is initiated by donor T cells distinct from classic cytotoxic T lymphocytes. 253 61

Cells required for the in vitro generation of syngeneic cytotoxic T-lymphocytes (CTL) against the P815 mastocytoma in the DBA/2 mouse strain were investigated. For both immune and tumor-bearing host spleen cells, CTL effector cells were eliminated by treatment with anti-Thy1.2, anti-Lyt1.1, or anti-Lyt2.1 and C', but were resistant to anti-L3T4 (GK1.5). Thus, CTL effectors (and their precursors) were Lyt1+2+, L3T4-. However, P815-specific CTL could not be generated in the absence of L3T4+ cells, whose function could be replaced with exogenous interleukin-2 (IL-2). When monoclonal antibodies against L3T4 were added to mixed leukocyte tumor cultures, CTL generation was markedly inhibited. Depletion of accessory cells also led to a marked reduction in CTL generation, which could be restored to control levels by adding adherent cells from normal spleens or with exogenous IL-2, but not with IL-1. Thus, accessory cells are apparently required to present the tumor antigens of this Ia-negative tumor to T-helper cells.
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PMID:Phenotype of syngeneic tumor-specific cytotoxic T-lymphocytes and requirements for their in vitro generation from tumor-bearing host and immune spleens. 296 66

To clarify the immune mechanism in myocarditis, we examined by immunofluorescence techniques the serial changes in percentages of T and B lymphocytes in the heart, spleen, and peripheral blood of DBA/2 mice inoculated with encephalomyocarditis (EMC) virus (experiment I). B cells were demonstrated by staining with fluorescein isothiocyanate (FITC)-labeled rabbit antimouse immunoglobulin (Ig). T cells were demonstrated with rat anti-Thy1.2 monoclonal antibody plus FITC-labeled antimouse Ig. There was a marked decrease in T cells in peripheral blood and a moderate decrease in the cells in the spleen on day 14. There were no significant changes in B cells in peripheral blood or spleen throughout the entire period and T cells accounted for approximately 80% of the cells in the myocardium on days 7 and 14. To confirm the involvement of T cells in the development of myocarditis, we also carried out studies in which BALB/c-nu/nu mice (group 1, n = 58), BALB/c-nu/+ mice (group 2, n = 54), and BALB/c-nu/nu mice injected with 5 X 10(7) spleen cells from BALB/c-nu/+ mice (group 3, n = 50) were inoculated with EMC virus (experiment II). Four mice from each of the three groups were killed on day 6 for virologic studies. In experiment II, there were no significant differences in the incidence of myocarditis among the three groups. Virus titrations of the heart and serum neutralizing antibody titers did not show any significant differences between the three groups on days 6 and 16.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunologic behavior of lymphocytes in experimental viral myocarditis: significance of T lymphocytes in the severity of myocarditis and silent myocarditis in BALB/c-nu/nu mice. 298 78

To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the lymph nodes with the functional assays measuring cytotoxic and tumor cell membrane-bound antibodies in mouse sera. Regional and non-regional (RLN, NRLN) lymph nodes, were subjected to stereological analysis to determine the volume fractions (Vv) of the cortex (C), the paracortex (PCA), the germinal centers (GC), and the medulla (M), using a computerized analysis system (IBAS I, Kontron). In both RLN:s and NRLN:s, lymphocyte subsets were identified and their ratios determined using the ABC (avidin-biotin peroxidase complex) technique and following monoclonal antibodies; Anti-Thy 1.2, Anti-Lyt 1, Anti-Lyt 2, and Anti-I-Ad. The 51Cr release assay was used to test the mouse sera for cytotoxic antibodies, and an indirect immunofluorescence (IF) technique to assess the sera for tumor cell membrane-bound antibodies. There was a marked enlargement of the RLN:s reaching the peak on day 12, due to increase of the Vv of the B-zone as well as of the T-zone. Evidence of distinct B-cell stimulation by the growing of P815X2 was provided by an early decrease of Thy1.2+/I-Ad+ cell ratio both in the RLN:s and in NRLN:s. This activation of B-cells seems to be parallel to the elevation of Lyt1+/Lyt2+ ratio in T-cell region on day 6. The IF-tests for or the presence of tumor cell membrane-bound antibodies were almost invariably negative. With exception of two sera, the 51Cr-release assay for cytotoxic antibodies against P815X2 targets was negative. The present study confirms the previous observations on failure to find circulating cytotoxic or cell membrane-bound antibodies in DBA/2 mice bearing P815X2 mastocytoma, despite the morphologically well definable activation in RLN:s and in NRLN:s of the B-cell areas. This is in alignment with the findings in the majority of human tumors, where B-cell predominance in RLN:s does not represent a favourable prognostic sign.
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PMID:Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. I. Morphometric assessment of lymph node immunoreactivity and analysis of circulating antibodies. 309 73

To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the thymus and spleen with the functional assays measuring cytotoxic (51Cr-release assay) and tumor cell membrane-bound antibodies (IF test) as well as phenotyping (with monoclonal antibodies Anti-Thy1.2, Anti-Lyt1, Anti-Lyt2, and Anti-I-Ad) the lymphocyte subsets in peripheral blood. The volume fractions (Vv) of the cortex (C), and medulla (M) of the thymus, as well as central (C-PALS) and peripheral periarteriolar lymphoid sheath (P-PALS) in the spleen were determined morphometrically. There was a steady increase of the C/M ratio from the control levels until day 8, not accompanied by any major fluctuations in the percentages of Thy1.2+ or I-Ad+ cells in C and M. In M, two significant peaks were found in Lyt1+/Lyt2+ cell ratio. In the spleen P-PALS, Thy1.2+/I-Ad+ cell ratio was subject to major early elevation, followed by a rapid and permanent decline to levels below the controls. Two high peaks of Lyt1+/Lyt2+ ratio were found in P-PALS, on day 10 and 16. In the C-PALS, a marked decline in Thy1.2+/I-Ad+ ratio was observed throughout the experiment. As determined by Vv, there was a marked early enlargement of P-PALS reaching the peak on day 4, and followed by a steady reduction reaching the control values on day 10. In peripheral blood, there was an initial increase of T-cells, leading to elevated Thy1.2+/I-Ad+ ratio and a subsequent elevation of Lyt1+/Lyt2+ ratio on day 8.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. II. Morphometric assessment of immunoreactivity in the thymus and spleen related to lymphocyte subsets in peripheral blood. 309 74

A number of cell surface markers (T200, ThB, Thy1, Lyt1 and Lyt2 and a glycolipid) and enzymes (ATP-ase, acid phosphatase, beta-glucuronidase, 5'-nucleotidase, non-specific esterase, ANAE and chloroacetate esterase) were determined for two murine T-cell lymphomas: the DBA/2-strain-derived SL2 with a phenotype close to that of a mature thymocyte and the GRS-strain-derived GSRL13 with a phenotype of a more primitive thymocyte. While the pattern of expression of the enzymes was similar for SL2 and GRSL13 and as such indistinguishable from that of the majority of thymus cells, the pattern of cell surface antigen expression was clearly different. GRSL12 cells express the ThB antigen and a glycolipid antigen detectable with monoclonal antibody 30-H11, but not Lyt1 and Lyt2 antigens. SL2 cells, however, do not express ThB and the glycolipid antigen, but do express Lyt1 and Lyt2.
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PMID:Cell surface antigen phenotypes and enzyme expression patterns of two murine T-cell lymphomas derived from early and/or mature thymus cells. 698 39


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