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

Nine children with severe combined immunodeficiency were treated in Lyon and Saint-Etienne. Two children had adenosine deaminase deficiency; another presented with a "bare lymphocyte syndrome", i.e. combined immunodeficiency associated with lack of expression of HLA-A and -B antigens on lymphocytes. Five children were treated with a transplant of genotypically HLA-identical bone marrow. The other 4 children received a transplant of foetal liver and foetal thymus from the same donor, as no compatible bone marrow donor was available. Seven of the 9 patients are still alive, reconstitution of the immune system being complete in 4 and incomplete in 3, and these results have been maintained throughout the years following transplantation. The only 2 failures were due to severe, widespread BCG infection, which had developed and persisted for several months before treatment. The measures now available for the treatment of infants with severe combined immunodeficiency are frequently successful in a disease previously lethal within a few months. They also contribute to our knowledge of lymphocyte differentiation and functions.
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PMID:[Treatment of severe combined immunodeficiency with bone marrow or foetal liver transplants (author's transl)]. 699 58

The role of HLA antigens in lymphocyte differentiation is strongly suggested by the existence of a recently identified immunodeficiency associated with, and probably resulting from, the lack of expression of HLA-A, B, and C antigens as well as beta2 microglobulin on various cells of hematopoietic origin. This "bare lymphocyte syndrome" has been described in a family where the transmission appeared to be autosomal recessive, and the responsible gene was not borne by the sixth chromosome. Another infant with a severe combined immunodeficiency disease has been treated with fetal liver and thymus transplants (FLTT). A persisting chimerism has been documented: T cells derived from the donor and B cells from the host. Despite complete HLA-A, B, and DR mismatch, T and B cells did cooperate resulting in significant antibody production, and defense against viral infection has been normal. Such an observation may suggest that "allogeneic restriction" of T-cell effector functions can be circumvented.
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PMID:Immunodeficiency diseases and expression of HLA antigens. 702 90

The use of the simian immunodeficiency virus (SIV) macaque model for assessing human immunodeficiency virus vaccine strategies will be facilitated by the characterization of predominant SIV cytotoxic T-lymphocyte (CTL) epitopes and their restricting major histocompatibility complex (MHC) class I molecules in macaque species. We now define a rhesus monkey SIVmac CTL epitope in the third hypervariable region of the envelope glycoprotein of the virus. This epitope, YNLTMKCR, contains the first two amino acids of a cysteine-cysteine loop which is the SIVmac analog of the human immunodeficiency virus type 1 V3 loop. We also employed one-dimensional isoelectric focusing to characterize the MHC class I molecule of the rhesus monkey that binds this SIVmac envelope peptide fragment. Cloning and sequencing the cDNA encoding this rhesus monkey MHC class I molecule demonstrates that it is a newly described HLA-A homolog, Mamu-A*02. This viral CTL epitope and its restricting MHC class I molecule will facilitate the use of the SIVmac rhesus monkey model for studies of envelope-based vaccine strategies and for exploring AIDS immunopathogenesis.
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PMID:A simian immunodeficiency virus envelope V3 cytotoxic T-lymphocyte epitope in rhesus monkeys and its restricting major histocompatibility complex class I molecule Mamu-A*02. 752 21

Initial studies suggested that major histocompatibility complex class I-restricted viral epitopes could be predicted by the presence of particular residues termed anchors. However, recent studies showed that nonanchor positions of the epitopes are also significant for class I binding and recognition by cytotoxic T lymphocytes (CTLs). We investigated if changing nonanchor amino acids could increase class I affinity, complex stability, and T-cell recognition of a natural viral epitope. This concept was tested by using the HLA-A 0201-restricted human immunodeficiency virus type 1 epitope from reverse transcriptase (pol). Position 1 (P1) amino acid substitutions were emphasized because P1 alterations may not alter the T-cell receptor interaction. The peptide with the P1 substitution of tyrosine for isoleucine (I1Y) showed a binding affinity for HLA-A 0201 similar to that of the wild-type pol peptide in a cell lysate assembly assay. Surprisingly, I1Y significantly increased the HLA-A 0201-peptide complex stability at the cell surface. I1Y sensitized HLA-A 0201-expressing target cells for wild-type pol-specific CTL lysis as well as wild-type pol. Peripheral blood lymphocytes from three HLA-A2 HIV-seropositive individuals were stimulated in vitro with I1Y and wild-type pol. I1Y stimulated a higher wild-type pol-specific CTL response than wild-type pol in all three donors. Thus, I1Y may be an "improved" epitope for use as a CTL-based human immunodeficiency virus vaccine component. The design of improved epitopes has important ramifications for prophylaxis and therapeutic vaccine development.
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PMID:Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. 754 95

The immune competence of peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus-seropositive (HIV+) patients was studied by assessing cytotoxic T lymphocyte (CTL) activity following recall HIV antigen stimulation. Target cells were HLA-A-matched EBV-transformed B cells expressing HIV-1 antigen. In the presence of recombinant IL-2 (rIL-2, 2 or 10 U/ml), about 50% of PBMCs from HIV+ asymptomatic patients responded to HIV-1 antigen stimulation in vitro with increased cytotoxic activity. In contrast, PBMCs from patients with overt AIDS, cultured in medium containing rIL-2 (2 U/ml) and HIV-1 antigen, showed no increase in cytotoxic activity; in the presence of rIL-2 (10 U/ml) and HIV-1 antigen, an inhibitory effect on CTL activity was observed. This inhibitory effect was associated with programmed cell death (apoptosis) of CD8+ lymphocytes and cells of both gamma/delta TcR-positive and -negative phenotypes. However, prior to the apoptosis, different TcR phenotypes of T lymphocyte reacted differently to HIV-1 antigen stimulation. The HIV-1 antigen initially appeared to cause gamma/delta TcR-positive T lymphocytes to proliferate and/or differentiate and later induced cell death. Whereas, prior to the apoptosis, no proliferation of gamma/delta TcR-negative T lymphocytes induced by HIV-1 antigen was observed.
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PMID:Programmed cell death induced by HIV type 1 antigen stimulation is associated with a decrease in cytotoxic T lymphocyte activity in advanced HIV type 1 infection. 774 39

We examined the role of endogenously produced interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in lectin-induced nonspecific suppressor activity in vitro. The cultures consisted of highly purified T lymphocytes, autologous monocytes and phytohemagglutinin (PHA). Kinetic studies revealed peak levels for both TNF-alpha and IL-1 beta production 4 hr after initiation of cultures which then declined and reached minimal levels on day 3. At this time point maximal levels of interleukin-2 (IL-2) were detected which declined sharply 24 hr later. The decline in cytokine levels in culture supernatants was most probably due to their consumption by the mononuclear cells which were found to express specific receptors for IL-1 beta, (IL-1 beta R), TNF-alpha (TNF-alpha R) and IL-2 (IL-2R) after 3- and 6-days of culture. After their first cycle of production and consumption both monokines were reproduced and the events followed the same patterns as for the first cycle: both monokines were first produced and at the time point of their consumption, IL-2 production reached maximal levels. The requirement for IL-1 beta and TNF-alpha in both IL-2 production and generation of suppressor activity was shown by three different approaches which included (a) blocking of HLA-DR molecules on monocytes which prevented monokine consumption during the early stages of culture, (b) blocking of HLA-A,B,C molecules on monocytes which prevented monokine consumption and IL-2 production late in culture, and (c) neutralization of monokine activity late in culture which resulted in highly reduced IL-2 production. T lymphocytes harvested from such cultures exhibited diminished suppressor activity. Our data suggest that the generation of nonspecific suppressor cell activity in vitro represents a complex system that requires cell interactions via self-major histocompatibility complex (MHC) antigen recognition and two cycles of cytokine production, where IL-1 beta and TNF-alpha production and consumption is a prerequisite for IL-2 production. Since lectin-induced nonspecific suppressor activity in vitro is deficient in certain autoimmune disorders the data presented herein might help in understanding the cellular basis for this immunodeficiency.
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PMID:On the role of monokines in the generation of nonspecific suppressor T cell activity in vitro. 807 8

With the development of chimeric simian-human immunodeficiency virus (SHIV)-infected macaques as a model for assessing novel human immunodeficiency virus type I (HIV-1) envelope glycoprotein (Env)-based vaccine strategies for preventing HIV-1 infection in man, it will be important to determine HIV-1 Env-specific cytotoxic T-lymphocyte (CTL) responses in vaccinated and virus-infected monkeys. To facilitate performing such CTL studies, we have defined two HIV-1 Env CTL epitopes in SHIV-infected rhesus monkeys and characterized the major histocompatibility complex (MHC) class I alleles that bind these Env peptide fragments and present them to CTL. A 9-amino-acid (aa) fragment of HIV-1 gp4l (p6B, aa 553 to 561) is presented to CD8+ CTLs of SHIV-infected animals by the rhesus monkey HLA-B homolog molecule Mamu-B*12. An 8-aa HIV-1 gpl.20 peptide (p9CD, aa 117 to 124) represents a CTL epitope in rhesus monkeys restricted by the HLA-A homolog MHC allele Mamu-A*08. This gp120 CTL epitope is fully conserved in all simian immunodeficiency virus, HIV-1, and HIV-2 isolates that have been sequenced to date and exhibits functional cross-reactivity. Screening of 14 unselected rhesus monkeys for expression of the two novel MHC class I alleles revealed the presence of each of the alleles in more than 40% of the animals. The characterization of the two HIV-1 Env CTL epitopes and their restricting MHC class I alleles will provide a basis for studying vaccine- and virus-elicited cytotoxic effector cell responses in rhesus monkeys.
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PMID:Definition of human immunodeficiency virus type 1 gp120 and gp41 cytotoxic T-lymphocyte epitopes and their restricting major histocompatibility complex class I alleles in simian-human immunodeficiency virus-infected rhesus monkeys. 879 94

The bare lymphocyte syndrome (BLS) consists of an association between a combined immunodeficiency disease and a significantly reduced expression of either human histocompatibility leukocyte antigens (HLA) class I (HLA-A, -B, -C) or HLA class II (HLA-DP, -DQ, -DR) at the cell surface. BLS type III, the more frequent form of this syndrome, is characterized by impaired expression of both class I and class II antigens on patients' cells, in particular on leukocytes. We describe herein the demonstration that expression of HLA class I molecules was reduced by approximately half on Epstein-Barr virus-transformed B cells (LCL) derived from type III BLS patients. HLA class I mRNA level was also decreased to the same extent. Expression of HLA class I molecules was also very significantly reduced at the surface of these fibroblasts as was mRNA specific for HLA class I. Simultaneously, the expression of HLA-DR molecules on LCL was even more greatly decreased, and the expression of HLA-DQ antigens was virtually abolished. Molecular analysis demonstrated an absence of mRNA for the alpha- and beta-chains of HLA-DQ and HLA-DR in the patients' lymphocytes. In general, such patients present with an association of an absence of expression of HLA class II antigens and a significantly reduced expression of HLA class I antigens. The mechanism of this association is still uncertain.
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PMID:Type III bare lymphocyte syndrome: lack of HLA class II gene expression and reduction in HLA class I gene expression. 895 82

We investigated the association between the phenotypes of human leucocyte antigens (HLA) class I on the surface of lymphocytes and serum concentrations of soluble HLA (sHLA) in normal and Human immunodeficiency virus (HIV) infected subjects. Serum concentrations of sHLA inn normal subjects with HLA-A 24 were significantly higher than those in such subject without HLA-A 24. The similar relation was found in HIV infected subjects whose levels of sHLA significantly increased compared with that of normal subjects. These results might suggest that the mechanism which causes the increase in secretion of sHLA in HIV infected subjects does not change the association between HLA phenotype and serum concentration of sHLA.
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PMID:[A study of the association between HLA phenotype and serum concentration of soluble HLA class I]. 917 67

Evaluation of human immunodeficiency virus type 1-specific mucosal cytotoxic T lymphocytes can be hampered by limited cell yields from mucosal sites. We sought to characterize virus-specific CD8(+) T lymphocytes with cytotoxic activity in the male genital tracts of SIVmac-infected rhesus monkeys by using a peptide epitope-specific functional T-cell assay and a tetrameric major histocompatibility complex class I-peptide complex. This tetrameric complex was constructed with the rhesus monkey HLA-A homolog molecule Mamu-A*01 and a dominant-epitope 9-amino-acid fragment of SIVmac Gag (p11C, C-M). The proportion of tetramer-positive CD8(+) T cells in semen of SIVmac-infected monkeys ranged from 5.9 to 22.0%. By the use of a standard 51Cr release assay, these cells were found to have peptide epitope-specific cytolytic activity after in vitro expansion. Four-color flow-cytometric analysis of these seminal tetramer-positive CD8(+) T cells demonstrated that they express memory-associated (CD62L- CD45RA-) and activation-associated (CD11a+ Fas+ HLA-DR+) molecules. The present experiments illustrate the power of tetramer technology for evaluating antigen-specific CD8(+) T lymphocytes in a mucosal tissue compartment.
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PMID:Detection of simian immunodeficiency virus Gag-specific CD8(+) T lymphocytes in semen of chronically infected rhesus monkeys by cell staining with a tetrameric major histocompatibility complex class I-peptide complex. 1019 57


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