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)

To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp 160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use.
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PMID:Construction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types. 171 88

A large number of human immunodeficiency virus type 1 (HIV-1) specific HLA-restricted cytotoxic T cell (CTL) epitopes have been mapped, including an HLA-B27-restricted immunodominant epitope within p25gag. Accordingly, this segment of the HIV-1 provirus was amplified by the polymerase chain reaction from DNA derived from fresh uncultured peripheral blood mononuclear cells (PBMC) of four HLA-B27 HIV-1-infected individuals. In all cases the majority of infected PBMC bore sequences encoding the HLA-B27-restricted peptide. CTL escape mutants had not accumulated in vivo 8 and 14 months later despite demonstrable CTL activity in vitro. These data emphasize the importance of silently infected lymphocytes in evading immune surveillance.
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PMID:In vivo persistence of a HIV-1-encoded HLA-B27-restricted cytotoxic T lymphocyte epitope despite specific in vitro reactivity. 171 89

The absence of long term bone marrow cultures for studying the growth and differentiation of human B cell precursors (BCP) has placed restrictions on the ability to analyze the early stages of human B cell ontogeny. We now describe a bone marrow-derived adherent cell microenvironment that maintains human BCP for several weeks in vitro. The adherent cells are maintained in a serum-free tissue culture medium, and consist of a predominant population of CD10+ fibroblast-like cells and a minor population of CD10+/nonspecific esterase+ macrophages. Adherent cell cultures seeded with fresh or cryopreserved fetal bone marrow, or purified CD10+/surface IgM- cells, provide a supportive microenvironment for lymphoid cells with a predominant phenotype of CD10+/CD19+/HLA-DR+/surface IgM-. Supplementation of the adherent cell cultures with human IL-7 induces active growth of BCP during the first 14 to 21 days of culture. However, the expansion of these cells does not continue past 21 days, and the cultures undergo a steady decline in BCP. Analysis of adherent cell conditioned medium revealed the presence of an unidentified soluble factor (or factors) that acts in concert with IL-7 to promote the growth of CD10+/surface IgM- cells. This culture system will be useful in elucidating the patterns of gene expression and growth factor requirements that characterize normal human B cell ontogeny, and perturbations of normal B cell ontogeny that lead to immunodeficiency and leukemia.
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PMID:Development of a bone marrow culture for maintenance and growth of normal human B cell precursors. 171 75

A HLA-A3.1-restricted CD8+ cytotoxic T-cell clone, E7.20, that lyses cells infected with human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 768-778 (RLRDLLLIVTR, NL43 env sequence) of the cytoplasmic domain of gp41 by successive use of a panel of recombinant vaccinia viruses that express truncated env genes and synthetic peptides. The epitope is conserved on 7 (NL43, BRU, HXB2, BRVA, SC, JH3, and JFL) of 13 human immunodeficiency virus type 1 isolates from North America. Synthetic peptides of this region of strains RF and CDC4 are also recognized by E7.20 despite a nonconservative Thr----Val or Thr----Ala change at amino acid 777; however, an MN peptide, which has four amino acid substitutions, was not reactive. The epitope recognized by E7.20 has a predicted hydrophobic alpha-helical structure, with three contiguous Leu residues followed by Ile and Val at amino acids 772-776. Cytotoxicity was restricted by HLA-A3.1 using allogeneic target cells that shared HLA class I antigens with the donor and an HLA-A and -B negative human plasma cell line transfected with the HLA-A3.1 gene. The transfected cells were infectable by human immunodeficiency virus type 1 strains IIIB and MN but only the former virus sensitized them to killing by E7.20. The ability of E7.20 to specifically lyse a human lymphocyte line infected with a human immunodeficiency virus type 1 strain carrying the conserved epitope is consistent with an important role for cytotoxic T cells in controlling infection.
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PMID:Specific lysis of human immunodeficiency virus type 1-infected cells by a HLA-A3.1-restricted CD8+ cytotoxic T-lymphocyte clone that recognizes a conserved peptide sequence within the gp41 subunit of the envelope protein. 171 55

To investigate the influence of HLA specificities on the rate of progression and outcome of human immunodeficiency virus (HIV) infection, we performed (a) a case-control study in 1989-1990 of HIV-seropositive individuals stratified by both risk behavior and ethnic background, (b) a longitudinal cohort study of HIV-infected male homosexuals enrolled in 1981-1982, and (c) an analysis of individuals with a diffuse infiltrative CD8 lymphocytosis syndrome. In the case-control study, there was a significantly higher frequency of HLA-B35 among intravenous drug users, but not homosexuals, who developed illnesses meeting the case definition for AIDS compared with asymptomatic HIV-positive controls, regardless of ethnic status. In the longitudinal study, HLA-B35-positive homosexuals had a significantly increased rate of progression to AIDS and decreased survival over a 7-year period compared with those without this specificity. Finally, there was a significantly decreased frequency of HLA-B35 in individuals with the diffuse infiltrative lymphocytosis syndrome, a clinically and genetically distinctive disorder occurring in HIV infection in which a low rate of progression to opportunistic infections was found. The high rate of salivary and lacrimal gland lymphoma in this group suggests that there is dissociation between the presence of HLA-B35 and the development of particular AIDS-defining conditions. We conclude that HLA-B35 is a risk factor for more rapid progression to AIDS, particularly opportunistic infections and Kaposi's sarcoma, operating in groups with high rates of newly acquired HIV infections such as New York City male homosexuals in 1981-1982, and intravenous drug users in 1989-1990.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA-B35 is associated with accelerated progression to AIDS. 173 86

We have previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV 1 gp41 (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies raised against synthetic peptides from these homologous regions bound not only to the isolated peptides, but also to "native" HLA class II molecules on cells. Screening of sera from HIV 1 infected individuals revealed high frequency of sera (35%) containing anti-class II crossreactive antibodies (CRAb), not only in AIDS patients, but also in early, asymptomatic patients. The CRAb containing sera caused potent inhibition of normal CD4-bearing cells' proliferative responses to tetanus toxoid in vitro. They could also kill class II bearing cells by ADCC. The possible contribution of these antibodies to the establishment of immunodeficiency state in HIV 1 infected individuals and/or to disease progression, was examined in two clinical studies: I. Asymptomatic patients were tested in parallel for their PBL responses to flu/tetanus, HLA alloantigens, and PHA (proliferation and IL2 production), and for the presence of anti-class II CRAb. About 50% of these patients showed a selective loss of their in vitro responses to recall antigens (flu/tetanus), which depend on CD4+ cells, while still responding to PHA and ALLO. Interestingly, positive correlation was found (P less than 0.001) between patients' lack of responsiveness to flu/tetanus and the presence in their sera of anti-class II CRAb. II. Retrospective study of HIV 1-infected hemophiliacs, suggest that patients with high titers of CRAb early in the disease progressed faster to full blown disease.
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PMID:Common sequence in HIV 1 GP41 and HLA class II beta chains can generate crossreactive autoantibodies with immunosuppressive potential early in the course of HIV 1 infection. 180 76

We report the outcome of a non-T-cell-depleted bone marrow transplant from an HLA partially incompatible, MLR-positive, parental donor in a patient with an unusual form of immunodeficiency characterized by a lack of CD8 T cells and a failure of the CD4 cells to display functional activity in vitro. Without conditioning, and following a mild and transient GVHD, donor T cells persist in trace amounts in the host, where they coexist with the nonfunctional host T cells and cooperate with host APC in antigen recognition, thereby leading to a reconstitution of T cell functions in vitro and in vivo and development of a stable, so far unprecedented, human T-T split chimera across MHC barriers.
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PMID:Coexistence of donor and host T lymphocytes following HLA-different bone marrow transplantation into a patient with cellular immunodeficiency and nonfunctional CD4+ T cells. 183 94

Primary membrane T cell immunodeficiencies (ID) have recently been characterized. In this paper we describe the main findings about the leukocyte adhesion deficiencies (LAD), the ID with low expression of the T cell receptor/CD3 complex, and the Omenn's syndrome. LAD is a consequence of mutations in the beta-chain-encoding gene of the leukocyte adhesion proteins. Functional consequences mainly affect phagocytic cells which are incapable of transendothelial migration. Effector T lymphocyte functions are, however, also impaired, i.e., helper T cell activity and cytotoxicity. The latter defect may account for the inability of LAD patients to reject HLA nonidentical bone marrow. Low expression of the T cell receptor CD3 complex is a rare entity characterized by a profoundly diminished expression of the whole complex on all T cells. The basic defect has not yet been unravelled. Interestingly, such T cells differentiate normally and can be activated by some antigens while anti-CD3 and anti-CD2 antibodies are not efficient. In five patients with Omenn's syndrome (combined immunodeficiency with eosinophilia), oligoclonal T cells were detected in blood, skin, and gut. These T cells are also in vivo activated. Since in one family, one sibling presented with typical SCID, i.e., alymphocytosis, and another with the Omenn's syndrome, it is proposed that the latter syndrome may correspond to a form of leakiness of SCID as found in the mice SCID model.
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PMID:Primary membrane T cell immunodeficiencies. 183 82

We have characterized CD4-CD8- double-negative (DN) alpha beta TCR+ T cells from a patient with immunodeficiency, lymphocytosis, lymphadenopathy, and hepatosplenomegaly. The majority of peripheral blood lymphocytes were DN alpha beta TCR+ T cells as evaluated by FACS and biochemical analysis. The DN T cells showed the following phenotype: alpha beta TCR+, gamma delta TCR-, CD2+, CD3+, CD4-, CD5+, CD7-, CD8-, CD16-, CD25-, CD26-, CD28+, CD45RO-, CD45RA+, CD57+, and HLA-DR+. Both southern blot analysis of TCR genes and FACS analysis applying a panel of V beta and V alpha monoclonal antibodies (MoAbs) indicated a polyclonal T-cell expansion. Thymic biopsy showed normal histology, whereas lymph node biopsy samples showed altered histological and immunohistological patterns with markedly expanded paracortical areas containing the DN T cells of the same phenotype as found in peripheral blood T cells. In functional studies, the DN T cells showed a profoundly reduced proliferative response upon stimulation with mitogens as well as MoAbs against the TCR/CD3 complex, CD2, and CD28, respectively. Addition of exogenous interleukin-2 (IL-2) only minimally augmented the proliferative response. In contrast, the addition of a combination of Ca2+ ionophore and phorbol 12-myristate 13-acetate (PMA) restored the proliferative response of the DN T cells to almost normal levels. This observation strongly suggests that the protein kinase C activity of the DN T cells was intact, but that the normal mechanism for transmembrane signal transduction was impaired in these unusual DN T cells.
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PMID:Phenotypical and functional characterization of double-negative (CD4-CD8-) alpha beta T-cell receptor positive cells from an immunodeficient patient. 183 26

To evaluate whether host genotype influences disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1), molecular techniques were used to determine genotypes at immune response loci for 114 HIV-1-infected homosexual/bisexual white men in the San Francisco Men's Health Study. Candidate genes evaluated were HLA-DQA1 and -DRB1, complement C4A and C4B, alpha- and beta-interferons, and the heavy chain of immunoglobulin gamma 1. Of the 114 men, 29 were asymptomatic, 21 were symptomatic men and AIDS patients (p = 0.02). Specifically, the HLA haplotype DRB1*0702-DQA1*0201 was associated with absence of symptoms (p = 0.003). Conversely, the frequency of the complement C4B-L allele was higher among patients with symptoms or with AIDS than among asymptomatic subjects (p = 0.02). These results suggest that genes in or near the major histocompatibility complex may influence the rate of disease progression among HIV-1-infected men.
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PMID:Influence of host genotype on progression to AIDS among HIV-infected men. 185 93


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