Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1)-infected SCID-hu thymic implants depleted of CD4(+) cells can support renewed thymopoiesis derived from both endogenous and exogenous T-cell progenitors after combination antiretroviral therapy. However, successful production of new thymocytes occurs transiently. Possible explanations for the temporary nature of this thymic reconstitution include cessation of the thymic stromal support function, exhaustion of T-cell progenitors, and viral resurgence. Distinguishing between these processes is important for the development of therapeutic strategies aimed at reconstituting the CD4(+) T-cell compartment in HIV-1 infection. Using an HIV-1 strain engineered to express the murine HSA heat-stable antigen surface marker, we explored the relationship between HIV-1 expression and CD4(+) cell resurgence kinetics in HIV-1-depleted SCID-hu implants following drug therapy. Antiviral therapy significantly suppressed HIV-1 expression in double-positive (DP) CD4/CD8 thymocytes, and the eventual secondary decline of DP thymocytes following therapy was associated with renewed viral expression in this cell subset. Thymocytes derived from exogenous T-cell progenitors induced to differentiate in HIV-1-depleted, drug-treated thymic implants also became infected. These results indicate that in this model, suppression of viral replication occurs transiently and that, in spite of drug therapy, virus resurgence contributes to the transient nature of the renewed thymic function.
 ...
PMID:Reconstitution of human thymic implants is limited by human immunodeficiency virus breakthrough during antiretroviral therapy. 1040 Jul 28

Phenotypic analysis of the medullary-type CD4+ CD8- [CD4 single-positive (SP)] thymocytes has revealed phenotypic heterogeneity within this cell population. The characteristic phenotype of mature peripheral T cells can be uniquely marked as Qa-2+ HSA- CD69-, whereas in the medullary-type CD4 SP thymocytes, the expression patterns of many markers were quite different. This suggests that there are many subgroups in the population, which reflects that medullary-type CD4 SP thymocytes may undergo phenotypic maturation. According to the results of two-colour flow cytometry, seven discrete phenotypes were identified by the expression capacity of Qa-2, HSA, CD69, 3G11 and 6C10 molecules. Consequently, the phenotypic precursor-progeny relationship can be envisaged as: 3G11- 6C10+ CD69+ HSAhi -->3G11+ 6C10+ CD69+ HSAhi --> 3G11+ 6C10- CD69+ HSAint -->3G11+ 6C10- CD69- HSAint Qa-2- -->3G11+ HSA-/lo Qa-2lo. At the stage of 3G11+ 6C10- CD69- HSAint Qa-2-, a branch pathway could be initiated, which gave rise to 3G11- HSAl degrees Qa-2- cells, which then, in turn, developed into 3G11- HSA-/loQa-2hi cells, a minor subgroup of the most mature CD4 SP cells. Consistent with this predicted pathway, experiments indicated that the first two subgroups were still cortisone sensitive, whereas the others were cortisone resistant. The cells in the last two Qa-2-positive subgroups are probably ready for emigration into the periphery.
 ...
PMID:Phenotypic identification of the subgroups of murine T-cell receptor alphabeta+ CD4+ CD8- thymocytes and its implication in the late stage of thymocyte development. 1045 21

The Hodgkin's-like Type B neoplasms which arise spontaneously in aging C57L mice (25% incidence at 21 months of age) were first reported over 40 years ago, but since then relatively little has been published about these lymphomas. Based on previous studies in SJL mice, we investigated the phenotypic and functional properties of C57L-derived lymphomas in relation to Mtv29-encoded vSAg expression by the tumor cells, and their ability to stimulate TCR Vbeta-restricted T cells. The cell surface phenotype of the C57L lymphomas indicates a B cell origin (sIg(+), MHC II(+)). These B lymphoma cells also express co-stimulatory molecules [B7-1 (CD80) and HSA (CD24)], and stimulate marked proliferation of syngeneic CD4(+) T cells. C57L B lymphoma cells exhibit Mtv-encoded mRNA by northern analysis, and also stimulate IL-2 production from Vbeta16(+) T cell hybrids, suggesting a role for Mtv 29 in this syngeneic T cell response. After transfer to syngeneic recipients, primary C57L lymphomas grow slowly, if at all. However, tumor growth is greatly accelerated by pretreatment of C57L recipients with anti-asialo GM1 antibody (but not anti-CD8 mAb), suggesting that NK cells play a major role in inhibiting lymphoma growth. If, in addition to anti-asialo GM1, the mice are also pretreated with anti-CD4 mAb, tumor growth is markedly inhibited, indicating that the lymphoma-responsive syngeneic CD4(+) T cells promote tumor growth. Therefore, although the vSAg-induced response stimulated by vSAg29 expressing lymphoma cells in syngeneic TCR Vbeta-restricted CD4(+) T cells is an important etiologic factor in this type of B cell neoplasm both in C57L and in SJL mice, the final outcome of the spontaneous neoplastic process appears strongly influenced by endogenous NK activity in aging mice.
 ...
PMID:B cell lymphomas of C57L/J mice; the role of natural killer cells and T helper cells in lymphoma development and growth. 1097 82

The functional maturation process of medullary-type CD4(-)CD8(+) [CD8 single-positive (SP)] thymocytes remains largely uncharacterized. We describe a phenotypic analysis of CD8 SP medullary-type thymocytes and find a remarkable heterogeneity within this thymic cell population. While mature CD8(+) T cells in the periphery are relatively homogeneous (TCRalphabeta(+)CD3(+)Qa-2(+) HSA(-)3G11(-)6C10(-)CD69(-)), CD8 SP medullary-type thymocytes contain discrete subpopulations that can be identified by differential expression of several cell-surface markers. We have identified at least six discrete subpopulations in the subset of TCRalphabeta(+)CD3(+) CD8 SP cells in the thymus. According to the expressed phenotypes, a linear developmental pathway is predicted among these CD8 SP subpopulations as follows: 6C10(+)CD69(+)HSA(hi)3G11(+)Qa-2(-) --> 6C10(-)CD69(+)HSA(hi/int)3G11(+)Qa-2(-) --> 6C10(-)CD69(-)HSA(int)3G11(+)Qa-2(-) --> 6C10(-)CD69(-)HSA(lo)3G11(+)Qa-2(-) --> 6C10(-)CD69(-)HSA(-/lo)3G11(-)Qa-2(-) --> 6C10(-)CD69(-)HSA(-/lo)3G11(-)Qa-2(+). This study provides a framework for understanding CD8 SP T cell maturation in the thymic medulla.
 ...
PMID:Heterogeneity within medullary-type TCRalphabeta(+)CD3(+)CD4(-)CD8(+) thymocytes in normal mouse thymus. 1122

The zinc finger transcription factor GATA-3 is of critical importance for early T cell development and commitment of Th2 cells. To study the role of GATA-3 in early T cell development, we analyzed and modified GATA-3 expression in vivo. In mice carrying a targeted insertion of a lacZ reporter on one allele, we found that GATA-3 transcription in CD4(+)CD8(+) double-positive thymocytes correlated with the onset of positive selection events, i.e., TCRalphabeta up-regulation and CD69 expression. LacZ expression remained high ( approximately 80% of cells) during maturation of CD4 single-positive (SP) cells in the thymus, but in developing CD8 SP cells the fraction of lacZ-expressing cells decreased to <20%. We modified this pattern by enforced GATA-3 expression driven by the CD2 locus control region, which provides transcription of GATA-3 throughout T cell development. In two independent CD2-GATA3-transgenic lines, approximately 50% of the mice developed thymic lymphoblastoid tumors that were CD4(+)CD8(+/low) and mostly CD3(+). In tumor-free CD2-GATA3-transgenic mice, the total numbers of CD8 SP cells in the thymus were within normal ranges, but their maturation was hampered, as indicated by increased apoptosis of CD8 SP cells and a selective deficiency of mature CD69(low)HSA(low) CD8 SP cells. In the spleen and lymph nodes, the numbers of CD8(+) T cells were significantly reduced. These findings indicate that GATA-3 supports development of the CD4 lineage and inhibits maturation of CD8 SP cells in the thymus.
 ...
PMID:Enforced expression of GATA-3 during T cell development inhibits maturation of CD8 single-positive cells and induces thymic lymphoma in transgenic mice. 1144 Oct 75

Two strains of human immunodeficiency virus type 1 (HIV-1) expressing different reporters, human placental alkaline phosphatase (PLAP) and murine heat stable antigen (HSA, CD24), were used for dual infection. Flow cytometric analysis enabled us to distinguish cells not only infected with individual reporter virus but also superinfected with both reporter viruses. When the CD4 positive T cell line, PM1, was dually infected by both reporter viruses with different coreceptor utilization, coinfection with CXCR4-tropic HIV-1 (X4 HIV-1) expressing one reporter increased the rate of cells infected with HIV-1 expressing another reporter. This enhancement was accompanied by an increased level of p24 antigen Gag in culture supernatant, indicating that infectivity of HIV-1 was augmented by X4 HIV-1 coinfection. The CXCR4 antagonist, T140 eliminated this enhancement, suggesting the role of X4 envelope via CXCR4. These results imply the role of X4 HIV-1 at the late stage of infection.
 ...
PMID:Enhanced infectivity of HIV-1 by X4 HIV-1 coinfection. 1292 5

Programmed death receptor 1 (PD-1) is expressed on thymocytes in addition to activated lymphocyte cells. Its ligation is thought to negatively regulate T cell activation, and PD-1(-/-) mice develop autoimmunity. To study the role of PD-1 on the development and function of a monoclonal CD8(+) T cell population, 2C TCR-transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice were generated. Unexpectedly, approximately 30% of peripheral T cells in these mice were CD4/CD8 double negative (DN). Although the DN cells were not activated by Ag-expressing APCs, they functioned normally in response to anti-CD3/anti-CD28. These cells had a naive surface phenotype and lacked expression of NK1.1, B220, and gammadelta TCR; and the majority did not up-regulate CD8alphaalpha expression upon activation, arguing that they are not predominantly diverted gammadelta-lineage cells. The thymus was studied in detail to infer the mechanism of generation of DN peripheral T cells. Total thymus cellularity was reduced in 2C TCR-transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice, and a relative increase in DN cells and decrease in double-positive (DP) cells were observed. Increased annexin V(+) cells among the DP population argued for augmented negative selection in PD-1(-/-) mice. In addition, an increased fraction of the DN thymocytes was HSA negative, suggesting that they had undergone positive selection. This possibility was supported by decreased emergence of DN PD-1(-/-) 2C cells in H-2(k) bone marrow chimera recipients. Our results are consistent with a model in which absence of PD-1 leads to greater negative selection of strongly interacting DP cells as well as increased emergence of DN alphabeta peripheral T cells.
 ...
PMID:Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells. 1456 31

The Runx family of transcription factors is thought to regulate the differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates Runx3 in CD4 silencing, but does not necessarily prove its role in the differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created transgenic mice that overexpress Runx3 and analyzed the development of thymocytes in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a TCR(high)HSA(low) phenotype. These cells were released from the thymus and contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-) cells in the spleen. Runx3 overexpression also increased the number of mature CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in mice with a class I-deficient background, both of which are favorable for CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression.
 ...
PMID:Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage. 1572 69

Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon, is a known immunomodulator. At high doses, BaP is immunosuppressive but at low doses it can enhance the immune response. Studies were conducted to determine if BaP would exacerbate the development of autoimmune disease in genetically prone NZB/WF1 mice. Five week old female NZBW/F1 mice were exposed dermally to 5, 20 and 40 mg/kg BaP for 30 days. Vehicle mice were exposed to an acetone:olive oil mixture for 30 days. BaP did not increase total IgG, anti-DNP-HSA or anti-dsDNA antibody levels. However, hematological evaluation revealed a decrease in erythrocyte number, hemoglobin and hematocrit and an increase in mean corpuscular volume and red cell distribution width in the 20 and 40 mg/kg dose groups. Liver and spleen weights were increased in the high dose groups; however, an increase in spleen cell number was not observed. Histopathological evaluation revealed splenic red pulp expansion in a mouse treated with 40 mg/kg BaP. An increase in splenic CFU-e production was observed in mice treated with 20 and 40 mg/kg BaP. A decrease in splenic total B cells, total T cells, CD4(+) and CD8(+) T cells was observed in mice treated with 20 and 40 mg/kg BaP. An increase in splenic null cells (non-T, non-B cells) was also observed in the high dose groups, consistent with extramedullary hematopoiesis. Coombs' tests, flow cytometry and an immune-mediated hemolysis assay indicated that the anemia was not autoimmune-mediated. Although no change was observed in the percentage of reticulocytes in these animals, further bone marrow analysis is needed to determine if the anemia is due to bone marrow suppression, possibly caused by BaP exposure, or chemical-induced hemolysis, perhaps contributed to by erythrocyte fragility inherited from a parent strain, NZB, which spontaneously develops autoimmune hemolytic anemia and subsequent splenomegaly.
 ...
PMID:Benzo(a)pyrene-induced anemia and splenomegaly in NZB/WF1 mice. 1593 65

The Kruppel-like factor, KLF13, is a member of a family of transcription factors shown to be involved in haematopoietic development. Here we show that KLF13 is involved in the development of B and T cells at multiple stages. Expression of KLF13 in the thymus was maximal in the DP population and in KLF13(-/-) deficient mice there was an accumulation of DP thymocytes and reduction of CD4(+)SP cells. Cell-surface expression of CD3(high), CD8, CD5 and HSA were altered on KLF13(-/-) DP cells, consistent with a defect in TCR signalling and at the DP to SP transition in KLF13(-/-) mice. KLF13 is also expressed in peripheral T-cells and peripheral T cell activation was impaired in KLF13(-/-) mice. Analysis of early B cell development in the bone marrow (BM) revealed a partial arrest of B cells at the transition from CD43(+) to CD43(-) pre-B cell, a transition that requires signalling through the pre-BCR. The proportion of IgM(+)/IgD(+) mature B cells was also increased in the BM of the KLF13(-/-) mice. This finding is consistent with a reduction in the strength of BCR signal or an accumulation of recirculating B cells from the periphery. Analysis of splenocytes isolated from KLF13(-/-) mice revealed an increase in the expression of CD21 and CD23 on B220(+) B cells, demonstrating a negative regulatory role for KLF13 in co-regulation of expression of CD21 and CD23. Thus KLF13 is involved at multiple different checkpoints in development that require signalling through the TCR, pre-BCR or mature BCR.
 ...
PMID:KLF13 influences multiple stages of both B and T cell development. 1860 72


<< Previous 1 2 3 4 5 6 Next >>