Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stimulation of peripheral blood mononuclear cells (PBMC) with allogeneic PBMC (ALLO) can result in activity that inhibits the replication of human immunodeficiency virus (HIV). The present study demonstrates that strong anti-HIV activity is dependent on expression of HLA-A*02 by the responding PBMC. Anti-HIV activity was equally effective against 2 primary isolates that use different coreceptors. Neither ALLO-stimulated cell proliferation nor cytokine and beta-chemokine production was associated with the expression of HLA-A*02. ALLO-stimulated production of strong anti-HIV activity required intact PBMC and was not inhibited by monoclonal antibodies directed against nonpolymorphic regions of human leukocyte antigens (HLAs). Anti-HIV activity was generated by ALLO-stimulated CD4(+) cells, CD8(+) T lymphocytes, and monocytes from HLA-A*02-positive patients. These findings provide the first evidence that the production of an HIV inhibitory factor or factors is associated with certain HLA genes and raise new possibilities concerning the role of the major histocompatibility complex in controlling viral infections via alloantigen stimulation.
 ...
PMID:Generation of alloantigen-stimulated anti-human immunodeficiency virus activity is associated with HLA-A*02 expression. 1113 72

Umbilical cord blood (UCB) is being increasingly used for hematopoietic stem cell transplantation and has been associated with a reduced incidence of severe graft-versus-host disease (GVHD). To further investigate the relative merits of unrelated donor UCB versus bone marrow (BM), a matched-pair analysis comparing the outcomes of recipients of 0 to 3 human leukocyte antigen (HLA)-mismatched UCB and HLA-A, B, DRB1-matched BM was performed. UCB patients, who received cyclosporine (CSA) and methylprednisolone (MP), were matched for age, diagnosis, and disease stage with BM patients, who received either methotrexate (MTX) and CSA (26 pairs) or T-cell depletion (TCD) and CSA/MP (31 pairs). Patients were predominantly children (median age, 5 years) undergoing transplantation for malignancy, storage diseases, BM failure, and immunodeficiency syndromes between 1991 and 1999. Although neutrophil recovery was significantly slower after UCB transplantation, the probability of donor-derived engraftment at day 45 was 88% in UCB versus 96% in BM-MTX recipients (P =.41) and 85% in UCB versus 90% in BM-TCD recipients (P =.32), respectively. Platelet recovery was similar in UCB versus BM pairs. Furthermore, incidences of acute and chronic GVHD were similar in UCB and BM recipients, with 53% of UCB versus 41% of BM-MTX recipients alive (P =.40) and 52% of UCB versus 56% of BM-TCD recipients alive at 2 years (P >.80), respectively. These data suggest that despite increased HLA disparity, probabilities of engraftment, GVHD, and survival after UCB transplantation are comparable to those observed after HLA-matched BM transplantation. Therefore, UCB should be considered an acceptable alternative to HLA-matched BM for pediatric patients.
 ...
PMID:Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. 1134 17

CD8(+) T lymphocyte function specific for human cytomegalovirus (CMV) was evaluated in 14 patients infected with human immunodeficiency virus (HIV) receiving highly active antiretroviral therapy (HAART) and 26 CMV-seropositive donors without HIV infection. Fifty-seven percent of the HIV-infected group had CMV-specific cytolytic activity in freshly isolated peripheral blood mononuclear cells (PBMC) against targets expressing CMV pp65. Both interferon (IFN)-gamma secretion by CD8(+) T cells and the frequency of human leukocyte antigen (HLA)-tetramer-positive T cells in HLA-A*0201-positive HIV-infected subjects correlated with CMV-specific cytolysis. In contrast, PBMC from healthy CMV-seropositive donors did not have either measurable CMV-specific cytolysis or secretion of IFN-gamma without in vitro stimulation. The T helper response to CMV antigens was vigorous in healthy CMV-seropositive donors but low in the cohort of HIV-infected patients. Potent CD8(+) cytotoxic T lymphocyte responses to CMV in HIV-infected patients receiving HAART is the converse of what is found in healthy CMV-seropositive subjects and may be the predominant adaptive immune response against CMV in HIV-infected patients.
 ...
PMID:Human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy maintain activated CD8+ T cell subsets as a strong adaptive immune response to cytomegalovirus. 1144 50

The human major histocompatibility complex (MHC), or human leukocyte antigen (HLA) region, encompasses over 4 Mb of DNA on the short arm of chromosome 6 and is traditionally divided into the class I, class II and class III regions. The MHC has now been entirely sequenced and ~220 genes have been defined of which ~62 are in the class III region. It is becoming clear that many of the latter encode proteins that are likely to be involved in the immune and inflammatory responses. The MHC is known to contribute to a large number of immune-related disorders including insulin dependent diabetes mellitus, rheumatoid arthritis, common variable immunodeficiency and IgA deficiency and there is growing evidence that genes within the class III region are important in determining susceptibility to many of these complex conditions. Genes in the class III region have also been implicated in a number of non-immune-related diseases such as congenital adrenal hyperplasia and sialidosis. Now that the full gene content of the class III region is known the stage is set for the identification and characterisation of candidate disease genes, which will allow greater understanding of the causes of many MHC-linked diseases and thus aid the development of improved treatments.
 ...
PMID:Genetic organization of the human MHC class III region. 1148 76

DNA vaccine involves the injection of plasmid DNA encoding an antigen under the control of an eukaryotic promoter, and results in cellular and humoral immune responses to the plasmid DNA-encoded antigen. The immune response induced by DNA vaccine usually has a T-helper-1(Th1) bias through a potent Th1-promoting adjuvant effect of immunostimulatory DNA sequences with CpG motifs present in plasmid DNA. It has been demonstrated that volunteers who were vaccinated with plasmid DNA encoding a malaria protein or a human immunodeficiency virus protein developed antigen-specific, human leukocyte antigen(HLA)-restricted, CD8+ cytotoxic T lymphocytes(CTLs) The demonstration in humans of the induction of CD8+ CTLs by DNA vaccines, including CTLs, provides a foundation for further clinical application of this potentially revolutionary vaccine technology.
 ...
PMID:[DNA vaccine]. 1151 28

The safety and immune effects of low-dose thalidomide treatment (3 mg/kg/day for 28 days) were evaluated in a study involving 8 South African human immunodeficiency virus (HIV)-infected children. The children were 7-69 months old and in disease stages A1-C3. Thalidomide therapy did not affect virus load, even though none of the children was receiving antiretroviral therapy. Thalidomide stimulated CD8+ T cells in peripheral blood, which increased expression of the activation markers CD38 and human leukocyte antigen DR and of the memory cell marker CD45RO. The frequency of HIV gag-specific CD8+ T cells in peripheral blood increased in 3 of 4 children who were evaluated during treatment with thalidomide. Clinical adverse events were mild. In this study, thalidomide was found to be safe and well tolerated and caused significant immunomodulation at a low dose. This is the first report describing use of an oral drug that may enhance HIV-specific CD8+ T cell function in HIV-infected children.
 ...
PMID:The immunomodulatory effects of thalidomide on human immunodeficiency virus-infected children. 1159 44

There is increasing evidence that CD8 lymphocytes may represent targets for infection by human immunodeficiency virus type 1 (HIV-1) in vivo whose destruction may contribute to the loss of immune function underlying AIDS. HIV-1 may infect thymic precursor cells destined to become CD4 and CD8 lymphocytes and contribute to the numerical decline in both subsets on disease progression. There is also evidence for the induction of CD4 expression and susceptibility to infection by HIV-1 of CD8 lymphocytes activated in vitro. To investigate the relationship between CD8 activation and infection by HIV-1 in vivo, activated subsets of CD8 lymphocytes in peripheral blood mononuclear cells (PBMCs) of HIV-seropositive individuals were investigated for CD4 expression and HIV infection. Activated CD8 lymphocytes were identified by expression of CD69, CD71, and the human leukocyte antigen (HLA) class II, the beta-chain of CD8, and the RO isoform of CD45. CD4(+) and CD4(-) CD8 lymphocytes, CD4 lymphocytes, other T cells, and non-T cells were purified using paramagnetic beads, and proviral sequences were quantified by PCR using primers from the long terminal repeat region. Frequencies of activated CD8 lymphocytes were higher in HIV-infected study subjects than in seronegative controls, and they frequently coexpressed CD4 (mean frequencies on CD69(+), CD71(+), and HLA class II(+) cells of 23, 37, and 8%, respectively, compared with 1 to 2% for nonactivated CD8 lymphocytes). The level of CD4 expression of the double-positive population approached that of mature CD4 lymphocytes. That CD4 expression renders CD8 cell susceptible to infection was indicated by their high frequency of infection in vivo; infected CD4(+) CD8 lymphocytes accounted for between 3 and 72% of the total proviral load in PBMCs from five of the eight study subjects investigated, despite these cells representing a small component of the PBMC population (<3%). Combined, these findings provide evidence that antigenic stimulation of CD8 lymphocytes in vivo induces CD4 expression that renders them susceptible to HIV infection and destruction. The specific targeting of responding CD8 lymphocytes may provide a functional explanation for the previously observed impairment of cytotoxic T-lymphocyte (CTL) function disproportionate to their numerical decline in AIDS and for the deletion of specific clones of CTLs responding to HIV antigens.
 ...
PMID:Activated peripheral CD8 lymphocytes express CD4 in vivo and are targets for infection by human immunodeficiency virus type 1. 1168 37

Receptors interacting with Major Histocompatibility Complex class I molecules have been initially found on the surface of human natural killer (NK) cells, where they deliver inhibitory signals to the lysis, being thus defined killer inhibitory receptors (KIR). Subsequently, they were detected also on the surface of T-CD8(+) lymphocytes and are particularly expanded during human immunodeficiency virus (HIV) infection, where they downregulate HIV-specific cytolysis. The expression of KIR recognizing human leukocyte antigen-C alleles was assessed in HIV-infected patients, undergoing highly active antiretroviral therapy (HAART). To this end, the combined expression of CD16/CD56, of CD3 and CD8 as well as of KIR (CD158a and CD158b) surface molecules was analyzed on peripheral blood mononuclear cells by monoclonal antibodies, and flow cytometry. An increase of CD3(+)CD8(+)CD158b(+) cells was found after 6 months of HAART. This finding may have implications for the regulation of T-cell mediated cytolysis during HAART.
 ...
PMID:Distribution of the natural killer-related receptor for HLA-C during highly active antiretroviral therapy for human immunodeficiency virus infection. 1175 1

It is very likely that perinatal human immunodeficiency virus type 1 (HIV-1) infection is influenced by a combination of virologic and host factors. A greater understanding of the role played by various risk factors for HIV-1 infection is crucial for the design of new preventive and therapeutic strategies. In recent years, a number of studies have suggested that host genetic factors are important determinants of both the susceptibility to perinatal HIV-1 infection and the subsequent pathogenesis of acquired immunodeficiency syndrome (AIDS). Control of HIV-1 infection involves the processing of specific viral peptides and their presentation to cells of the immune system by highly polymorphic human leukocyte antigen (HLA) alleles. The contribution of multiple HLA class I and II alleles in modulating pediatric HIV/AIDS outcomes has now been confirmed by several independent groups. Penetration of HIV-1 into cells is mediated by interaction between CD4 and chemokine receptors that serve as entry coreceptors. Genetic polymorphisms in chemokine ligand and chemokine receptor genes have recently been associated both with mother-to-child HIV-1 transmission and disease progression in children. These observations suggest a key role for genetic factors in pediatric HIV-1 infection. This article describes the current state of knowledge regarding host genetic influences on pediatric HIV-1 infection and discusses the role of these genes in HIV/AIDS pathogenesis.
 ...
PMID:Genetic determinants of pediatric HIV-1 infection: vertical transmission and disease progression among children. 1177 47

2F5 is one of the very few monoclonal antibodies with the capacity to neutralize a wide spectrum of type 1 human immunodeficiency virus (HIV-1) strains and primary isolates. Constructing an immunogen that contains a conformational mimic of the epitope recognized by 2F5 could provide the means to induce a broadly neutralizing anti-HIV-1 antibody response. Thus, in an effort to create a targeted, adjuvant-independent immunogen able to induce a 2F5-like antibody response, the gp41 sequence recognized by 2F5 (ELDKWAS) was genetically incorporated into different regions of an antibody specific for a framework determinant on human leukocyte antigen (HLA)-DR. All constructs were expressed, secreted from Sf9 insect cells, and found to retain the anti-HLA-DR specificity of the parental antibody. Three of the four constructs in which the ELDKWAS sequence was incorporated into a beta-turn (BT)-like conformational site were recognized by the 2F5 antibody. In contrast, none of the five constructs with the same sequence incorporated into surface-exposed regions of helical turn had any detectable 2F5 reactivity. In addition to demonstrating the significant plasticity of several regions in the antibody molecule in terms of accepting foreign sequences without loss of expression or binding specificity, these results also suggest that the native epitope recognized by the 2F5 antibody may be more beta-turn-like than helical in conformation. Importantly, with respect to vaccine development, the 2F5-reactive antibody constructs represent candidate immunogens for the adjuvant-independent induction of an HIV-1, neutralizing 2F5-like antibody response in humans.
 ...
PMID:Construction of recombinant targeting immunogens incorporating an HIV-1 neutralizing epitope into sites of differing conformational constraint. 1180 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>