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Biomedical subjects

C M Walker

Publications and source records attributed to C M Walker.

67 records · Page 4Linked to original sources
PubMed1989

A diffusible lymphokine produced by CD8+ T lymphocytes suppresses HIV replication.

Peripheral blood CD8+ T lymphocytes from human immunodeficiency virus (HIV)-infected individuals suppress replication of HIV in peripheral blood mononuclear cells (PBMC). This anti-viral activity appears to be mediated in part by a diffusible factor. Production of this lymphokine varies among infected individuals and may reflect the intrinsic ability of an individual's CD8+ cells to control HIV infection. In some cases in which factor activity is not apparent, contact of the CD8+ cells with infected CD4+ cells can produce for suppression of virus replication. These observations could lead to approaches for enhancing anti-viral responses in HIV-infected individuals.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Human immunodeficiency virus (HIV) from experimentally infected chimpanzees: isolation and characterization.

Human immunodeficiency virus-1 (HIV-1) isolates obtained from chimpanzees that had undergone various immunosuppressive treatments were characterized by growth on various primary cells and cell lines as well as by restriction endonuclease analysis. Viruses recovered from animals inoculated with uncloned HIV showed genetic variation from the original inoculum, whereas viruses isolated from an animal infected with a molecular clone of HIV did not. In some cases, virus recovery was possible only after enrichment for CD4+ cells by panning, inoculation with a chimpanzee cytomegalovirus, or a combination of these procedures. These findings indicate a role for viral and host cofactors in the control of virus replication and suggest explanations for the absence of clinical manifestations in HIV-infected chimpanzees.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Identification of human immunodeficiency virus (HIV) envelope type-specific T helper cells in an HIV-infected individual.

Two T helper cell clones recognizing the gp 120 envelope protein of HIV were generated from the peripheral blood of a healthy seropositive individual. These cells were type specific as they proliferated and produced IL 2 when stimulated by an epitope in the amino-terminal half of gp 120 of HIVSF2, but not by a similar region of HIVZr6, a Zairian HIV-1 isolate. These two viruses differ by 26% in the deduced amino sequence of the gp 120 protein. Moreover, the antigenic site(s) recognized by the cloned T cells are distinct from those recognized by envelope-specific antibodies. These observations have important implications for the development and use of anti-HIV vaccines.

Acquired Immunodeficiency Syndrome↗
PubMed1986

CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication.

Lymphocytes bearing the CD8 marker were shown to suppress replication of human immunodeficiency virus (HIV) in peripheral blood mononuclear cells. The effect was dose-dependent and most apparent with autologous lymphocytes; it did not appear to be mediated by a cytotoxic response. This suppression of HIV replication could be demonstrated by the addition of CD8+ cells at the initiation of virus production as well as after several weeks of virus replication by cultured cells. The observations suggest a potential approach to therapy in which autologous CD8 lymphocytes could be administered to individuals to inhibit HIV replication and perhaps progression of disease.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Abrogation of anti-Pichinde virus cytotoxic T cell memory by cyclophosphamide and restoration by coinfection or interleukin 2.

Previously, we demonstrated that memory cell-mediated immune responses can be generated in Pichinde virus (PV)-primed mice after secondary challenge in vivo with homologous virus. Further, treatment of mice with cyclophosphamide (CY) before primary infection with PV abrogated the generation of H-2-restricted, virus-specific cytotoxic T lymphocytes (CTL), and rechallenge of these mice was followed by neither a primary nor a secondary CTL response. Here, we demonstrate that this CY-induced block in memory anti-PV CTL generation was not due to establishment of a persistent infection. Interestingly, this CY-induced block in memory anti-PV CTL generation was overcome by secondarily coinfecting mice with PV and lymphocytic choriomeningitis virus (LCMV) or PV and Tacaribe virus. Secondary infection with LCMV or Tacaribe virus alone did not elicit anti-PV CTL. Coinfection resulted in the generation of a PV-specific memory CTL response as judged by maximal activity on day 4 after rechallenge. Co-infection with PV and vesicular stomatitis virus, an unrelated rhabdovirus, did not efficiently restore memory anti-PV CTL responses. Memory anti-PV CTL responses were also restored when interleukin 2 (IL 2)-containing supernatants were injected i.p. after rechallenge of CY-treated mice with PV. To demonstrate that IL 2 was the responsible lymphokine in these preparations, highly purified IL 2 was added to in vitro cultures of spleen cells from CY-treated PV-primed mice. In the presence of PV-infected syngeneic macrophages, addition of purified IL 2 resulted in a dose-dependent restoration of H-2-restricted anti-PV CTL activity. The CTL precursor (CTLp) frequency of CY-treated PV-primed mice was markedly decreased from that of normal PV-primed mice. Thus, the long-lasting block in the ability to generate a PV-specific memory CTL response after CY treatment appears to be due to both a lack of helper T cell activity and a significant reduction of CTLp. However, this block may be overcome by coinfecting with viruses that cross-react at the helper T cell level or by exogenous treatment with highly purified IL 2.

Animals↗
PubMed1984

Generation of memory cell-mediated immune responses after secondary infection of mice with pichinde virus.

Pichinde virus (PV), a member of the arenavirus group, was found to elicit strong cell-mediated immune responses in various strains of mice. After primary i.v. inoculation, augmentation of natural killer (NK) cell activity occurred and peaked 3 to 4 days after infection. The NK response was followed by a second peak of cytotoxic activity that was found to be H-2 restricted, virus specific, and mediated by Thy-1.2+, Lyt-2.2+ lymphocytes. This cytotoxic T lymphocyte (CTL) response peaked 7 days post infection. Neutralizing antibodies were not detectable after PV infection of the mice. In light of this, we investigated the generation and kinetics of secondary cell-mediated immune responses after reinjection of homologous virus in vivo. Slight but significant augmentation of NK activity was observed 1 day after secondary virus challenge. As in the primary response, effectors of this NK activity rapidly became sensitive to anti-Thy-1.2 and complement treatment. NK activity rapidly returned to background levels and was followed by an anamnestic CTL response that peaked 4 days after reinjection of the virus. Thus, cell-mediated immune responses appeared more rapidly after secondary challenge in vivo, and the temporal relationship between NK and CTL generation was maintained. Both secondary NK and CTL responses were generated in mice that had been pretreated with cyclophosphamide (CY), suggesting that memory cell-mediated immune responses can be reactivated in vivo without undergoing cell division. In contrast, treatment with CY before primary infection delayed the appearance of virus-induced NK activity and abrogated the generation of H-2-restricted virus-specific CTL. Rechallenge of these CY-treated NK-primed mice resulted in the rapid generation of a secondary NK response that was not followed by either a primary or secondary CTL response. The data suggest that cells mediating a nonspecific effector function may possess specific memory. We discuss our results with respect to possible NK-CTL relationships.

Animals↗
PubMed1976

A system for controlled microwave heating of small samples.

A system for the controlled thawing and heating of small samples in a waveguide is described. A means of maintaining constant absorbed power within the sample over a wide range of sample parameters is a major feature of the system. Provision for sensing the melting point of immersed samples is include. Samples are continuously rotated to improve heating uniformity.

Heating↗
PubMed1975

Increased activity of low-Km cyclic adenosine 3':5'-monophosphate phosphodiesterase in plasma membranes of Morris hepatoma 5123tc (h).

The total cyclic adenosine 3':5'-monophosphate (cAMP) phosphodiesterase activities as well as the activities of the low- and high-K-m enzyme forms were investigated in homogenates, 100,000 X g supernatants, and plasma membrane fractions of rat liver and Morris hepatoma 5123tc(h); the responsiveness of hepatoma and liver plasma membrane (low-K-m) phosphodiesterases to imidazole (40 mM) and theophylline (5mM) were also compared at cAMP concentrations of 1 and 7.5 muM. The total cAMP phosphodiesterase activities of tumor homogenates and 100,000 X g supernatant fractions were found to be less than one-half those of liver; kinetic studies of homogenates indicated that this finding was largely due to a substantial reduction (53%) in activity of the hepatoma high-K-m enzyme. In contrast, low-Km cAMP phosphodiesterase activities for tumor homogenate and plasma membrane fractions were significantly (50%) higher than liver; this was particularly evident when cAMP concentrations were between 0.5 and 2 muM. Since these concentrations are in the range of basal physiological levels of cAMP in hepatocytes, the present results suggest that the reduced levels of cAMP, previously observed in hepatoma 5123tc (h), are primarily due TO An increased rate of cAMP metabolism by low-Km cAMP phosphodiesterase in plasma membranes of the tumor. Imidazole increased the activity of the low-K-m cAMP phosphodiesterase of liver plasma membranes by 22 (1 muM cAMP) and 38% (7.5 muM camp); tumor activity was enhanced 35 and 50%, respectively, at 1 and 7.5 muM cAMP. Theophylline inhibited the plasma membrane phosphodiesterase activity of liver 79 and 53% at cAMP concentrations of 1 and 7.5 muM, respectively; hepatoma activity was inhibited 82 (1 muM cAMP) and 62% (7.5 muM cAMP).

Animals↗