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)

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

Experiments to identify cell determinants involved in HIV-1 tropism revealed a specific decrease in the expression of the T-cell activation antigen CD26 after monocytotropic (M-tropic) but not T-cell line-tropic (T-tropic) virus infection of the PM1 T-cell line. The level of CD26 expression in single-cell clones of PM1 correlated with the entry rate and cytopathicity of M-tropic HIV-1 variants, resulting in preferential survival of cells with low CD26 levels after infection. Experiments with recombinant viruses showed that the third hypervariable region of the envelope gp120 plays an important role in this selection process. This study identifies CD26 as a key marker for M-tropic human immunodeficiency virus type 1 (HIV-1) infection and suggests a mechanism for the early loss of CD26-expressing cells in HIV-1-infected individuals.
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PMID:CD26 expression correlates with entry, replication and cytopathicity of monocytotropic HIV-1 strains in a T-cell line. 758 8

Tryptase TL2 purified from MOLT-4 human T cells binds to the envelope protein of human immunodeficiency virus type 1 (HIV-1). Tryptase TL2 and CD26 antigen are supposed to play roles in HIV-1 entry into cells. Although CD4 is a principal receptor for HIV-1, brain cells expressing the CD4 antigen are not permissive to HIV-1 strains infectious to monocyte or T-cell lines. We examined whether the non-permissiveness of the brain-derived cells to standard HIV-1 strains could be explained by a lack of tryptase TL2 or CD26. Western blots showed that the amounts of tryptase TL2 expressed in cell lysates prepared from the brain-derived cells were similar to those prepared from various cells susceptible to HIV-1 strains. Furthermore, flow cytometry revealed the presence of the CD26 antigen on the cell surface of many types of cells. The resistance of the brain-derived cells to standard HIV-1 strains is not due to a lack of tryptase TL2 or CD26.
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PMID:Detection of tryptase TL2 and CD26 antigen in brain-derived cells non-permissive to T-cell line-tropic human immunodeficiency virus type 1. 782 28

The V3 loop of the gp120 of human immunodeficiency virus type 1 (HIV-1) is assumed to be involved in HIV-1-mediated membrane fusion. V3-derived peptides have been shown either to enhance or to prevent HIV-1 infection. Multibranched peptide constructs (MBPCs) derived from the V3 North American/European consensus sequence were designed to sort out these conflicting findings. At 5 microM, MBPC1 (8-branched GPGRAF) totally, and MBPC2 ([RKSIHIGPGRAFYT]4) partially, inhibited HIV-1LAI infection, whereas the GPGRAF monomer had only a limited effect. A peptide of the entire V3 consensus loop and a control MBPC had no detectable activity. The 5 microM MBPC1 HIV-1-inhibiting concentration was not cytotoxic, nor did it alter T lymphocyte allogeneic, antigen-, or mitogen-induced reactivities, and it was about 5- to 50-fold lower (MBPC2 and MBPC1, respectively) than that resulting in 50% cell death. Analysis of MBPC immunoreactivity showed that MBPC2, but not MBPC1, strongly reacted with human HIV-1 positive sera. Only MBPC2 elicited significant antibody responses in rabbits. The V3-derived MBPCs bound to CD4+ cells, as determined by immunofluorescence analysis. The binding was inhibited either by soluble CD4 or by CD4 monoclonal antibody (mAb) MT151, which recognizes the CDR3 region of the D1 domain of CD4, but not by other CD4 mAbs Leu3a, OKT4A, Q4021, 13B8-2, 5A8, RFT4, nor by the CD26 mAb BA5. Therefore, it appears likely that MBPCs inhibit HIV-1 infection by interacting with the CDR3 region of CD4 or with a region in its vicinity.
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PMID:Multibranched peptide constructs derived from the V3 loop of envelope glycoprotein gp120 inhibit human immunodeficiency virus type 1 infection through interaction with CD4. 783 1

The phorbol ester phorbol myristate acetate (PMA) strongly inhibits human immunodeficiency virus type 1 (HIV-1)-induced syncytium formation; it has been suggested that this inhibitory effect is due to the transient downmodulation of the surface-associated CD4 receptors by PMA (I. H. Chowdhury, Y. Koyanagi, S. Kobayashi, Y. Hamamoto, H. Yoshiyama, T. Yoshida, and N. Yamamoto, Virology 176:126-132, 1990). Surprisingly, PMA treatment of cells expressing truncated (A2.01.CD4.401) and hybrid (A2.01.CD4.CD8) CD4 molecules, which are not downmodulated (P. Bedinger, A. Moriarty, R. C. von Borstel II, N. J. Donovan, K. S. Steimer, and D. R. Littman, Nature [London] 334:162-165, 1988), inhibited their fusion with CD4- (12E1) cells expressing vaccinia virus-encoded HIV-1 envelope glycoprotein (gp120-gp41) and with chronically HIV-1-infected H9 (MN, IIIB, or RF) cells. PMA pretreatment of T (12E1) and non-T (HeLa, U937.3, and Epstein-Barr virus-transformed B) cell lines expressing vaccinia virus-encoded CD4 also blocked fusion with 12E1 cells expressing vaccinia virus-encoded gp120-gp41. Interestingly, pretreatment of the gp120-gp41-expressing 12E1 cells with PMA did not alter their fusion with untreated CD4-expressing cells. Although the inhibitory effect of PMA was rapid and treatment for 1.5 h with 5 ng of PMA per ml was sufficient to reduce fusion by more than 50%, the recovery after treatment was slow and more than 40 h was needed before the cells regained half of their fusion potential. The inhibitory effect of PMA was blocked by staurosporine in a dose-dependent fashion, suggesting that it is mediated by protein kinase C. PMA treatment of A2.01.CD4.401 cells reduced the number of infected cells 6.7-fold, as estimated by a quantitative analysis of the HIV-1 MN infection kinetics, probably by affecting the stage of virus entry into cells. CD26 surface expression was not significantly changed by PMA treatment. We conclude that PMA inhibits the CD4-gp120-gp41-mediated fusion by modulating an accessory component(s), different from CD26, in the target CD4-expressing cells. These findings suggest a novel approach for identification of accessory molecules involved in fusion and may have implications for the development of antiviral agents.
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PMID:The phorbol ester phorbol myristate acetate inhibits human immunodeficiency virus type 1 envelope-mediated fusion by modulating an accessory component(s) in CD4-expressing cells. 790 14

The immune dysfunction in human immunodeficiency virus (HIV) infection is complex and cannot be explained solely on the basis of numerical depletion of T lymphocytes. Inappropriate, uncontrolled activation of the immune system may be involved. In a test of this hypothesis, five HIV-infected children were prospectively treated with prednisone and selected immunologic and virologic indices were analyzed. Subjects had marked T lymphopenia (CD4+ T lymphocytes < 500 cells/ml) and antigenemia (serum p24 antigen > 30 pg/ml) and were free of opportunistic infections. There was a significant drop in serum p24 antigen concentrations from baseline (60.2 +/- 10.1% SEM; P < 0.005) 4 weeks after initiation of prednisone, which returned to baseline concentrations as the prednisone was tapered. Concomitant with this decrease, there was decreased expression of cell surface activation markers (HLA-DR, CD25 (interleukin 2 receptor) and CD26 (Ta-1)) in peripheral T lymphocytes. There was no significant change in either T lymphocyte subset numbers or mitogen and antigen-specific lymphoproliferation. A regulatory dysfunction of the immune system, allowing inappropriate activation of T lymphocytes, may be involved in the pathogenesis of HIV disease, and further studies involving selective immunosuppression in HIV disease are warranted.
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PMID:Immunologic and virologic effects of glucocorticoids on human immunodeficiency virus infection in children: a preliminary study. 790 39

The human immunodeficiency virus 1 (HIV-1) Tat protein suppresses antigen-induced, but not mitogen-induced, activation of human T cells when added to T-cell cultures [Viscidi, R. P., Mayur, K., Lederman, H. M. & Frankel, A. D. (1989) Science 246, 1606-1608]. This activity is potentially pertinent to the development of AIDS because lymphocytes from HIV-infected individuals exhibit a similar antigen-specific dysfunction. Here we report that Tat binds with high affinity to the T-cell activation molecule dipeptidyl aminopeptidase IV (DP IV), also known as CD26. This molecule occurs on the surface of CD4+ cells responsible for the recall antigen response and appears to play an essential role in this response. Tat binds to both the cell surface and soluble forms of DP IV at physiological salt concentrations without inhibiting the protease activity of DP IV against small chromogenic substrates used to assay activity, but Tat markedly inhibits the activity of DP IV at lower salt concentrations. The kinetics of inhibition indicate the affinity of Tat for DP IV varies from 20 pM to 11 nM, and the activity of the Tat-DP IV complex varies from 13% to 100%, as the NaCl concentration varies from 0 to 140 mM. Cytofluorometry experiments demonstrate that Tat competes with anti-Ta1, a monoclonal antibody (mAb) specific for DP IV, for binding to cell surface DP IV, thus indicating that Tat binds DP IV at or near the Ta1 epitope. Moreover, the anti-Ta1 mAb blocks the immunosuppressive activity of Tat. The high affinity of Tat for DP IV, previous evidence implicating DP IV in antigen-specific T-cell activation events, and the ability of anti-Ta1 mAb to block the immunosuppressive effect of Tat make DP IV a plausible receptor for Tat's immunosuppressive activity.
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PMID:Human immunodeficiency virus 1 Tat binds to dipeptidyl aminopeptidase IV (CD26): a possible mechanism for Tat's immunosuppressive activity. 791 30

It has been proposed recently that the cell surface peptidase CD26 acts in concert with CD4, the human immunodeficiency virus (HIV) primary receptor molecule, to mediate HIV entry into permissive cells. We have failed to detect significant levels of CD26 cell surface expression and enzymatic activity in a number of commonly propagated human CD4+ cell lines, although CD26 mRNA was present at very low levels, as detected by reverse transcription PCR. No relationship existed between the expression of CD26 and the ability of these cells to be infected with HIV or to fuse to form syncytia. We have tested two inhibitors of CD26 enzymatic activity and several anti-CD26 monoclonal antibodies and found that they inhibit neither HIV infection nor HIV-induced syncytium formation. NIH 3T3 cells stably transfected with the cDNAs for human CD4 and CD26 expressed these molecules at the cell surface and had CD26 enzymatic activity. Inoculation of the double transfectants with HIV did not result in virus entry above the background level, as verified by PCR amplification of viral DNA. We were unable to recover infectious virus from the HIV-inoculated NIH 3T3 double transfectants either by transfer of supernatants or by cocultivation with human CD4+ indicator cells. Moreover, the transfectants did not fuse with HIV-infected cells to form syncytia, nor were syncytia observed in HIV-inoculated cultures. These results are inconsistent with the CD26 molecule being a cofactor for entry of HIV in CD4+ cells.
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PMID:Factors involved in entry of the human immunodeficiency virus type 1 into permissive cells: lack of evidence of a role for CD26. 791 60

To examine the role of CD26/dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) in infection by human immunodeficiency virus type 1 (HIV-1), we utilized CD26 cDNA-transfected Jurkat T-cell lines. Both CD26- parental Jurkat cells and mutant CD26+ (DPPIV-) transfected Jurkat cells were readily infected with HIV-1, whereas wild-type CD26+ (DPPIV+) transfected Jurkat cells were more resistant to HIV-1 infection. Our results suggest that CD26 is not essential for HIV-1 infectivity as suggested by others but that DPPIV enzyme activity may decrease the efficiency of HIV-1 infection. Of great interest, we found that mutant CD26+ (DPPIV-) transfectants and CD26- parental Jurkat cells strongly expressed CD95 (Fas/Apo-1) and were more sensitive than wild-type CD26+ (DPPIV+) transfectants to the induction of apoptosis by anti-CD95 monoclonal antibody. These results suggest that CD26 may play a role in HIV-1-associated loss of -CD4+ cells through the process of programmed cell death.
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PMID:Role of CD26/dipeptidyl peptidase IV in human immunodeficiency virus type 1 infection and apoptosis. 793 26

Work in this laboratory previously demonstrated that the tropism of different human immunodeficiency type 1 isolates for infection of human CD4+ continuous cell lines (e.g., T-cell lines and HeLa-CD4 transformants) versus primary macrophages is associated with parallel intrinsic fusogenic specificities of the corresponding envelope glycoproteins (Envs). For T-cell line-tropic isolates, it is well established that the target cell must also contain a human-specific fusion cofactor(s) whose identity is unknown. In this study, we tested the hypothesis that the Env fusion specificities underlying T-cell line versus macrophage tropism are determined by distinct cell type-specific fusion cofactors. We applied a recombinant vaccinia virus-based reporter gene assay for Env-CD4-mediated cell fusion; the LAV and Ba-L Envs served as prototypes for T-cell line-tropic and macrophage-tropic isolates, respectively. We examined CD4+ promyeloctic and monocytic cell lines that are infectible by T-cell line-tropic isolates and become susceptible to macrophage-tropic strains only after treatment with differentiating agents. We observed parallel changes in fusion specificity: untreated cells supported fusion by the LAV but not the Ba-L Env, whereas cells treated with differentiating agents acquired fusion competence for Ba-L. These results suggest that in untreated cells, the block to infection by macrophage-tropic isolates is at the level of membrane fusion; furthermore, the differential regulation of fusion permissiveness for the two classes of Envs is consistent with the existence of distinct fusion cofactors. To test this notion directly, we conducted experiments with transient cell hybrids formed between CD4-expressing nonhuman cells (murine NIH 3T3) and different human cell types. Hybrids formed with HeLa cells supported fusion by the LAV Env but not by the Ba-L Env, whereas hybrids formed with primary macrophages showed the opposite specificity; hybrids formed between HeLa cells and macrophages supported fusion by both Envs. These results suggest the existence of cell type-specific fusion cofactors selective for each type of Env, rather than fusion inhibitors for discordant Env-cell combinations. Finally, analyses based on recombinant protein expression and antibody blocking did not support the proposals by others that the CD44 or CD26 antigens are involved directly in the entry of macrophage-tropic isolates.
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PMID:Cell type-specific fusion cofactors determine human immunodeficiency virus type 1 tropism for T-cell lines versus primary macrophages. 876 60


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