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)

In the present study we observed a significant depression of thymocytes during pregnancy and investigated the influences of this thymic change on the immunologic capacities of peripheral lymphocytes. Thymocytes in pregnant mice began to decrease in number from Day 10 and reached about 0.1-fold of the nonpregnant level at Day 19, just before parturition. At late stage of pregnancy, thymocyte subpopulation expressing CD4+CD8+ and Thy1.2+PNA+ was selectively depressed. On the contrary, peripheral lymphocytes including splenocytes, peripheral blood lymphocytes and peripheral lymph node cells showed no depression. As to the immunologic capacities of the pregnant hosts, delayed footpad reaction and phagocytic activity of fixed liver macrophages in vivo were remarkably suppressed, but MLR reactivity and antibody response to SRBC or haptens were well preserved. Transfer of pregnant sera or administration with steroid hormones especially E3 into nonpregnant mice induced similar changes in the thymus and peripheral lymphocytes in number and subsets but this could not mimic the immunologic reactivities of the pregnant mice. These results suggest that sex steroid hormones such as E3 play an important role in the changes in cell populations of each lymphoid organ and the immune reactivities of the hosts during pregnancy. However, other factors also contribute to the immunologic capacities of the maternal hosts.
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PMID:Thymic depletion in pregnancy: kinetics of thymocytes and immunologic capacities of the hosts. 166 37

Screening and analysis of immunotoxic and immunomodulatory activity has become an integral component in preclinical studies of pharmaceuticals and xenobiotics. In an attempt to replace laborious and expensive batteries of assays used at present we developed a multiple immunoassay (MIA) enabling the determination, in a single mouse, of: the weight of the thymus, spleen and a group of lymph nodes; delayed type hypersensitivity and antibody response to SRBC; phagocytic activity of peritoneal macrophages and the responsiveness of spleen lymphocytes to "T" (PHA, ConA) and "B" (LPS) mitogens in vitro. The MIA responsiveness to two prototype immunostimulators (Thymostimulin and Listeria factor Ei) was tested at two time periods after antigenic stimulation, not only in normal mice, but also in animals with selectively depressed T-systems (anti-Thy1.2 monoclonal antibody) and B-systems (cyclophosphamide); in both dexamethasone-treated and irradiated animals. The findings indicate, that this MIA is capable of reflecting both immunosuppressive and immunostimulatory activities of the tested agents and permits partial insight into the mechanisms underlying these activities.
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PMID:Preclinical screening and analysis of the immunotoxic and immunomodulatory activity using a multiple immunoassay (MIA) in mice. 210 13

In murine models of systemic lupus erythematosus and in many humans with SLE, antibodies against native DNA (dsDNA) are a major contributor to the pathogenesis of the disease. Loss of self-tolerance to the DNA antigen may be associated with B-cell defects or regulatory cell dysfunction. We have developed B-cell lines with specificity for the antigen DNA, from both the autoimmune BWF1 mouse strain and from the non-autoimmune BALB/c strain, to use in the investigation of inherent B-cell defects in autoimmunity. Six BWF1 cell lines and five BALB/c cell lines which are free of Thy1.2+ cells and esterase positive cells, and have between 35 and 89% rosetting with dsDNA-SRBC targets, have been propagated in vitro for 24-36 months. The cells are non-malignant, growth-factor dependent and have no antigen or mitogen in the growth medium. Lyt-1 positive cells are found in the cell lines, but Lyt-1 negative cells are also present. They respond to the antigen DNA-HRBC when EL-4 supernatant is present in culture, and the peak of the plaque-forming cell (PFC) response is the same for both strains. When cells from both strains are cultured with varying amounts of T-cell factors, there is no difference in spontaneous antibody-forming cell (AFC) formation or in response to anti-mu stimulation between BWF1 and BALB/c strains. BALB/c spleen cells do not respond to DNA-HRBC in this culture system, but BWF1 spleen cells, as well as cell line cells from both strains, respond to this antigen. T cells from non-responding BALB/c spleen and responding BWF1 spleen are able to suppress the immune response to DNA-HRBC of cell line B cells from both strains. Propagating B-cell lines in the presence of DNA for 2 weeks stimulates BWF1 cell line cells, but suppresses the response of BALB/c cell lines to antigen.
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PMID:Investigations of intrinsic abnormalities in DNA-specific B lymphocytes from autoimmune mice. 252 8

Immunomodulatory effects of cholera toxin (CT) were investigated in a murine model using various immunological parameters. C3H/HeN mice were injected with 2 micrograms of CT at various intervals (from 6 h to 21 days) before the immunological assays. Thymocytes were markedly decreased in their absolute number, and the phenotypes in such cells were clearly shifted from Thy1.2high+ PNAhigh+ to Thy1.2low+ PNAlow+ 2-4 days after the CT treatment. Spleen T cells were relatively increased, while surface IgM positive B cells were rather decreased. Natural killer activity and in vivo and in vitro cytotoxic T lymphocyte activity were markedly suppressed during the early stages after the CT treatment but recovered completely within 21 days. Mixed lymphocyte reaction was profoundly suppressed at least for the 1st week after the CT treatment. Furthermore, EL-4 tumor of C57BL/6 origin grew progressively and killed the recipient C3H mice when such tumor cells were inoculated 6 h after the CT treatment. On the contrary, a marked augmentation of direct (IgM) and indirect (IgG) plaque-forming cell responses to sheep red blood cells was seen after CT treatment. Delayed footpad reaction to SRBC was also augmented after CT treatment. As the mechanisms, both direct augmentation of CD4+ T cells and direct suppression of CD8+ T cells appeared to occur at a time due to the CT treatment. An indirect effect of CT through the release of the endogenous steroids was dismissed in the present study. Taken together, CT appears to have differential immunomodulatory effects on various immune effector cells through various mechanisms.
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PMID:Immunomodulatory effects of cholera toxin in mice. 279 14

Spontaneously hypertensive rats (SHR) which regularly develop hypertension and periarteritis nodosa showed a progressive loss of T cell numbers and functions early in life. When six months old and compared with W rats, the original strain of SHR, they were found to possess a reduced number of thymocytes that formed rosettes with guinea pig erythrocytes and that reacted to anti-Thy1. 1 and anti-T (W3/13) sera. The number of spleen and lymph node cells which reacted to anti-T (W3/13) and anti-helper T (W3/25) sera also decreased. The antibody response of 3-month-old SHR spleen cells to SRBC was about one-fifth that of Wistar rats and progressively declined with age. Subcutaneous grafting of 3-month-old SHR thymus tissues failed to promote differentiation and functions of T cells in the spleen of nude mice, whereas 3-month-old W thymus tissues showed significant recovery of T cell generation and functions. The T cell functions of old SHR was completely restored by grafting adult W thymus tissues but was not restored by grafting adult SHR thymus tissues. Similar recovery was also obtained by the injection of thymus extracts from W thymus tissues. These results suggest that thymic epithelial cell products regulating T cell maturation may decrease in SHR with increasing age.
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PMID:The arrest of T cell maturation in spontaneously hypertensive rats with a deficient production of thymic factors. 286 57

Graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (BMT), can be prevented by in vitro depletion of T cells from the bone marrow (BM) prior to transplantation. The purpose of this study was to assess the role of BMT cells in the reconstitution of various immune functions following BMT across minor histocompatibility barriers. Lethally irradiated CBA/J (H-2k) mice were grafted with either 10(7) unseparated or T-cell-depleted BM cells from B10.BR (H-2k, minor-histoincompatible) mice. Blood counts, BM colonies in agar, and various immune functions of spleen cells from the recipient mice were tested 2-12 weeks post-BMT and compared with those of normal donors. The following observations were made: (A) Peripheral blood lymphocyte counts decreased to 30% of normal 2 weeks post-BMT with almost normal recovery at 8 weeks. (B) The percentage of Thy1.2+ splenocytes reached normal levels at 8 weeks post-BMT. (C) The number of BM colonies (GM-CFU) was reduced to 10% at 2 weeks and fully recovered at 12 weeks. (D) Proliferative response to the B-cell mitogen LPS was fully reconstituted after 4 weeks; however, anti-SRBC PFC (following Mishell-Dutton cultures) was restored 50% at 8-12 weeks. (E) Reconstitution of T cell functions including proliferative responses to concanavalin A, phytohemagglutinin, and allogeneic leukocytes, and allocytotoxicity, did not exceed 50% even 12 weeks post-BMT. Overall, depletion of T cells from donor BM allografts incompatible at minor histocompatibility loci, did not seem to significantly alter the rate of immunohematopoietic reconstitution in the lethally irradiated BM recipients.
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PMID:Bone marrow transplantation with T-cell-depleted grafts. II. Reconstitution of immunohemopoietic functions in lethally irradiated mice transplanted with unseparated or T-cell-depleted bone marrow grafts disparate at minor histocompatibility antigens. 295 82

The Peyer's patches contain a large number of precursor cells committed to the production of immunoglobulin A (IgA) and play an important role in IgA response in the mucosal immune system. We investigated the induction of IgA producing cells in Peyer's patches by plaque forming cell assay after oral administration of a traditional Chinese herbal medicine, Xiao-chai-hu-tang (Japanese name: Shosaiko-to). The number of total IgA producing cells in the Peyer's patches detected by the protein-A plaque assay was increased about two-fold by Shosaiko-to administration and the numbers of both anti-SRBC and anti-HRBC IgA producing cells were also increased by such a treatment. On the other hand, when SRBC alone were administered orally, only the number of anti-SRBC IgA producing cells was increased. Further, we examined T-cell subpopulations in the gut-associated lymphoid tissues after oral administration of Shosaiko-to by flowcytometry. Marked alternations in T cell subpopulations were not detected in the Peyer's patches, though TcR gamma delta+T-cells in the intraepithelial lymphocytes and Thy1.2-TcR alpha beta+T cells in the mesenteric lymph nodes were slight increased. These results showed that orally administered Shosaiko-to acts as a polyclonal B-cell activator which induces IgA production in the mucosal immune system.
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PMID:Enhancement of immunoglobulin A production in Peyer's patches by oral administration of a traditional Chinese medicine, xiao-chai-hu-tang (Shosaiko-to). 834 52

A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal venous (PV) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV) injection of whole B6 BMCs 5 days after the PV injection (abbreviated as 5.5 Gy x 2 + PV + IV). All recipients survived more than 1 year after this treatment (more than 64 weeks after birth). Abnormal T cells (Thy1.2(+)/B220(+)/CD3(+)/CD4(-)/CD8(-)) present in MRL/lpr mice before the treatment disappear, and hematolymphoid cells are reconstituted with donor-derived cells. The treated mice are free from autoimmune diseases. Levels of autoantibodies (IgG/IgM anti-ssDNA antibodies and IgG/IgM rheumatoid factors) decrease to normal levels. Successful cooperation is achieved among T cells, B cells, and antigen-presenting cells (APCs) of the treated MRL/lpr mice when evaluated by in vitro anti-SRBC responses. Newly developed T cells are tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex (MHC) determinants. These findings clearly indicate that severe autoimmune diseases in MRL/lpr mice are completely ameliorated by the treatment without recourse to immunosuppressants, and that the treated MRL/lpr mice show normal immune functions, strongly suggesting that this strategy would be applicable to humans. (Blood. 2000;95:1862-1868)
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PMID:Treatment of intractable autoimmune diseases in MRL/lpr mice using a new strategy for allogeneic bone marrow transplantation. 1068 49