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)

The human immunodeficiency virus (HIV), the human T cell lymphotropic virus (HTLV-1), the human foamy retrovirus and the simian immunodeficiency viruses have been associated with the development of an inflammatory myopathy in humans and primates. The myopathy caused by HIV and HTLV-1 is not due to direct infection of the muscle by these viruses, but rather due to an immunopathologic process triggered by the viruses, mediated by autoaggressive CD8+ cells in the context of MHC-class I antigen expression. This has been based on a series of studies utilizing immunocytochemistry, in situ hybridization, polymerase chain reaction, and co-cultivation of human myotubes with the viruses or with HIV-1 and HTLV-1-infected homologous lymphoid cells. Because the clinical, histological and immunological picture of patients with retroviral-associated inflammatory myopathies is identical to that of patients with retroviral-negative inflammatory myopathy, there is a reasonable possibility that retroviruses may be candidate viruses in triggering inflammatory myopathies. In recent years, the antiretroviral drug AZT (Zidovudine), commonly used for the treatment of AIDS, has been shown to cause a distinct mitochondrial myopathy characterized by depletion of the muscle mitochondrial DNA due to AZT's ability to inhibit the gamma-DNA polymerase of the mitochondrial matrix. Distinction of the AZT-myopathy is clinically important because it responds to discontinuation of AZT and to administration of another antiretroviral agent such as ddI or ddC.
 ...
PMID:Retroviruses and inflammatory myopathies in humans and primates. 815 47

Immunotherapy of malignant tumors is often hampered by "immune escape" phenomenons of tumor cells. Both active (e.g. induction of T-cell apoptosis, secretion of immunomodulators, -downregulators) and passive (e.g. antigen shedding, loss of MHC-class I/II molecules on the tumor cell surface) mechanisms are involved in this process. Another reason are inborn or acquired immunodeficiency syndromes. Gene technology tries to reconstitute the immunocompetent status by genetic compensation or modulation of the defect. Some of these trials have been performed already in phase I studies of different kinds of tumors and will be shortly presented here.
 ...
PMID:[Genetic techniques to overcome antitumor anergy]. 1035 98

Human peripheral blood CD8+ T cells comprise cells that are in different states of differentiation and under the control of complex homeostatic processes. In a number of situations ranging from chronic inflammatory conditions and infectious diseases to ageing, immunodeficiency, iron overload and heavy alcohol intake, major phenotypic changes, usually associated with an increase in CD8+ T cells lacking CD28 expression, take place. CD8+CD28- T cells are characterized by a low proliferative capacity to conventional stimulation in vitro and by morphological and functional features of activated/memory T cells. Although the nature of the signals that give origin to this T-cell subset is uncertain, growing evidence argues for the existence of an interplay between epithelial cells, molecules with the MHC-class I fold and CD8+ T cells. The possibility that the generation of CD8+CD28- T cells is the combination of TCR/CD3zeta- and regulatory factor-mediated signals as a result of the sensing of modifications of the internal environment is discussed.
 ...
PMID:CD8+CD28- T cells: certainties and uncertainties of a prevalent human T-cell subset. 1186 57

CD8 T cells play an important role in controlling viral infections. We investigated the in situ localization of simian immunodeficiency virus (SIV)-specific T cells in lymph and genital tissues from SIV-infected macaques using MHC-class I tetramers. The majority of tetramer-binding cells localized in T cell zones and were CD8(+). Curiously, small subpopulations of tetramer-binding cells that had little to no surface CD8 were detected in situ both early and late post-infection, and in both vaginally and rectally inoculated macaques. These tetramer(+)CD8(low/-) cells were more often localized in apparent B cell follicles relative to T cell zones and more often found near or within the genital epithelium than the submucosa. Cells analyzed by flow cytometry showed similar populations of cells. Further immunohistological characterization revealed small populations of tetramer(+)CD20(-) cells inside B cell follicles and that tetramer(+) cells did not stain with gammadelta-TCR nor CD4 antibodies. Negative control tetramer staining indicated that tetramer(+)CD8(low/-) cells were not likely NK cells non-specifically binding to MHC tetramers. These findings have important implications for SIV-specific and other antigen-specific T cell function in these specific tissue locations, and suggest a model in which antigen-specific CD8+ T cells down modulate CD8 upon entering B cell follicles or the epithelial layer of tissues, or alternatively a model in which only antigen-specific CD8 T cells that down-modulate CD8 can enter B cell follicles or the epithelium.
 ...
PMID:Localized populations of CD8 MHC class I tetramer SIV-specific T cells in lymphoid follicles and genital epithelium. 1912 15

Lack of chronic immune activation in the presence of persistent viremia is a key feature that distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection in natural hosts from pathogenic SIV and HIV infection. To elucidate novel mechanisms downmodulating immune activation in natural hosts of SIV infection, we investigated natural killer T (NKT) lymphocytes in sooty mangabeys. NKT lymphocytes are a potent immunoregulatory arm of the innate immune system that recognize glycolipid antigens presented on the nonpolymorphic MHC-class I-like CD1d molecules. In a cross-sectional analysis of 50 SIV-negative and 50 naturally SIV-infected sooty mangabeys, ligand alpha-galactosylceramide loaded CD1d tetramers co-staining with Valpha24-positive invariant NKT lymphocytes were detected at frequencies >or=0.002% of circulating T lymphocytes in approximately half of the animals. In contrast to published reports in Asian macaques, sooty mangabey NKT lymphocytes consisted of CD8(+) and CD4/CD8 double-negative T lymphocytes that were CXCR3-positive and CCR5-negative suggesting that they trafficked to sites of inflammation without being susceptible to SIV infection. Consistent with these findings, there was no difference in the frequency or phenotype of NKT lymphocytes between SIV-negative and SIV-infected sooty mangabeys. On stimulation with alpha-galactosylceramide loaded on human CD1d molecules, sooty mangabey NKT lymphocytes underwent degranulation and secreted IFN-gamma, TNF-alpha, IL-2, IL-13, and IL-10, indicating the presence of both effector and immunoregulatory functional capabilities. The unique absence of CD4(+) NKT lymphocytes in sooty mangabeys, combined with their IL-10 cytokine-secreting ability and preservation following SIV infection, raises the possibility that NKT lymphocytes might play a role in downmodulating immune activation in SIV-infected sooty mangabeys.
 ...
PMID:Paucity of CD4+ natural killer T (NKT) lymphocytes in sooty mangabeys is associated with lack of NKT cell depletion after SIV infection. 2035 88

Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses.
 ...
PMID:Unusual antigen presentation offers new insight into HIV vaccine design. 3022 Mar 51

The pathogenesis in the majority of patients with common variable immunodeficiency (CVID), the most common symptomatic primary immunodeficiency, remains unknown. We aimed to compare the minor and major histocompatibility complex (MHC) markers as well as polygenic scores of common genetic variants between patients with monogenic CVID and without known genetic mutation detected. Monogenic patients were identified in a CVID cohort using whole exome sequencing. Computational full-resolution MHC typing and confirmatory PCR amplicon-based high-resolution typing were performed. Exome-wide polygenic scores were developed using significantly different variants and multi-variant Mendelian randomization (MR) analyses were used to test the causality of significant genetic variants on antibody levels and susceptibility to infectious diseases. Among 83 CVID patients (44.5% females), monogenic defects were found in 40 individuals. Evaluation of the remaining CVID patients without known genetic mutation detected showed 13 and 27 significantly associated MHC-class I and II alleles, respectively. The most significant partial haplotype linked with the unsolved CVID was W*01:01:01-DMA*01:01:01-DMB*01:03:01:02-TAP1*01:01:01 (P < 0.001), where carriers had a late onset of the disease, only infection clinical phenotype, a non-familial form of CVID, post-germinal center defects and a non-progressive form of their disease. Exclusion of monogenic diseases allowed MR analyses to identify significant genetic variants associated with bacterial infections and improved discrepancies observed in MR analyses of previous GWAS studies with low pleiotropy mainly for a lower respiratory infection, bacterial infection and Streptococcal infection. This is the first study on the full-resolution of minor and major MHC typing and polygenic scores on CVID patients and showed that exclusion of monogenic forms of the disease unraveled an independent role of MHC genes and common genetic variants in the pathogenesis of CVID.
 ...
PMID:Histocompatibility Complex Status and Mendelian Randomization Analysis in Unsolved Antibody Deficiency. 3203 58