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Biomedical subjects

H W Kreth

Publications and source records attributed to H W Kreth.

At least 73 records · Page 4Linked to original sources

Immunohistochemical identification of T-lymphocytes in the central nervous system of patients with multiple sclerosis and subacute sclerosing panencephalitis.

T-lymphocytes were identified in frozen brain sections derived from patients with chronic inflammatory disorders of the CNS by using a specific heteroantiserum and the unlabelled antibody enzyme method. Clusters of T-cells were found in post-mortem material of cases with multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE). The results suggest that T-lymphocytes are involved in the pathogenesis of both MS and SSPE.

Adolescent↗

Mumps virus replication in human lymphoid cell lines and in peripheral blood lymphocytes: preference for T cells.

The replication of mumps virus was studied in human continuous lymphoblastoid cell lines (LCLs) with T or B characteristics and in lymphocyte subpopulations derived from peripheral blood. T-LCLs supported effective virus replication as shown by high titers of free and cell-associated virus over 1 to 4 days after infection. By immunofluorescence analysis, the majority of cells were positive for mumps virus antigens. In contrast, the B-cell lines produced low titers of infectious virus, and only a small percentage expressed viral antigens. This resistance of the B-LCLs was found with several mumps virus strains. Cultures of peripheral blood mononuclear cells also supported mumps virus replication. Very high titers of infectious virus (10(8) PFU/ml) were observed in cultures prestimulated with phytohaemagglutinin. Studies with enriched T and B cells point to the activated T lymphocyte as the major virus-producing cell.

B-Lymphocytes↗

Demonstration of primary cytotoxic T cells in venous blood and cerebrospinal fluid of children with mumps meningitis.

Cryopreserved lymphocytes from venous blood and cerebrospinal fluid (CSF) of 10 children with mumps meningitis were tested in 5-hr 51Cr-release assays against uninfected and mumps virus-infected PHA-blasts. Lymphocytes from all patients were cytotoxic to autologous mumps virus-infected target cells, but completely failed to lyse histoincompatible virus-infected PHA-blasts. Cytotoxicity was specific for the infecting virus, and was mediated by E rosette-forming lymphocytes. The effector cells were present over 2 to 3 wk after onset of meningitis. Mumps viral antigens appeared to be preferentially recognized in association with HLA B determinants. The results show that specifically sensitized cytotoxic T cells (CTL) are induced in patients with mumps meningitis. These cells circulate in venous blood and are locally enriched in CSF. Based on clinical observations, it is proposed that mumps-specific CTL play an immunopathologic role.

Acute Disease↗

HLA restriction of secondary mumps-specific cytotoxic T lymphocytes.

Mumps virus-specific cytotoxic T lymphocytes (CTL) were induced by incubating peripheral lymphocytes from healthy blood donors with autologous mumps virus-infected stimulator cells. Maximum cytotoxicity was generated after 5 to 7 days in culture. No cytotoxic activity was induced in the absence of viral antigens. The cytotoxicity induced in vitro was a secondary immune response, because no specific lytic activity could be generated in lymphocyte cultures from mumps seronegative donors. The effector cells were restricted by the HLA complex in a "hierarchical" pattern. The major restriction antigens for secondary CTL were certain HLA B determinants such as B18, B27, Bw25, Bw62, and Bw63. Mumps responses in spite of high [3H]-thymidine uptake in sensitized cultures. The present data suggest that mumps virus-specific CTL may be directly regulated by certain genes of the HLA B locus.

Adolescent↗

Demonstration of HLA restricted killer cells in patients with acute measles.

The relationship between HLA determinants on effector and target cells and cell-mediated cytotoxicity was studied using the release of 51Cr from measles virus-infected PHA-blasts. HLA compatibility between effector and target cells was not required if effector lymphocytes were derived from measles seropositive adults, from a patient with SSPE, and from children after live measles vaccination. Cytotoxicity was always abolished after removal of Fc receptor-bearing lymphoid cells. In these donors, the effect is, therefore, probably due to K cells. In contrast, lymphocytes from children with acute measles preferentially killed those virus-infected target cells with which they shared HLA antigens. Selective lytic activity was still observed after elimination of Fc receptor-bearing lymphoid cells. It is suggested that HLA-dependent killer cells represent specific cytotoxic T lymphocytes. These cells seem to be limited to the acute phase of measles.

Acute Disease↗

Cell-mediated cytotoxicity against measles virus in SSPE. I. Enhancement by antibody.

In patients with subacute sclerosing panencephalitis (SSPE) virus persistency has been explained by a blocking factor of specific cell-mediated immunity in SSPE serum and cerebrospinal fluid (CSF). In the present study the effect of SSPE serum and CSF on cell-mediated cytotoxicity against 51Cr-labeled allogenic measles virus-infected target cells was tested. Pretreatment of SSPE peripheral lymphoid cells by serum or CSF neither blocked nor increased measles-specific cytotoxicity when cells were subsequently tested in FCS containing tissue culture medium. However, killing activity was always enhanced after pretreatment of target cells or direct addition of serum or CSF to the cytotoxic assay. Enhancement was also observed with non-SSPE-derived measles antibodies. The effect was dependent on measles antibody concentrations. These results suggest that antibody-dependent killing by K cells is intact in patients with SSPE. It is possible that virus-infected brain cells are protected from an immune attack in vivo by antibody-induced antigenic modulation.

Antibodies, Viral↗

Cell-mediated cytotoxicity against measles virus in SSPE. II. Analysis of cytotoxic effector cells.

An analysis of subacute sclerosing panencephalitis (SSPE) lymphocytes was performed in order to find out whether T or K cells were involved in killing of 51Cr-labeled allogeneic measles virus-infected target cells. Lymphocyte donors were three patients with SSPE, 10 measles seropositive controls and 2 children with measles rash. It was found that about 75% of measles-specific cytotoxicity was lost after removal of Fc-receptor-bearing cells by adsorption onto immune complex monolayers. K cell activity (as measured by lysis of 51Cr-labeled-sensitized chicken red blood cells) was reduced to the same extent. After adsorption, the enhancing effect by specific antibody was no longer observed. Unfractionated peripheral lymphoid cells that had been treated with pronase and kept in culture 24 hr were inactive in the cytotoxicity test when compared to freshly isolated cells. However, cytotoxicity could be restored almost completely by the addition of measles antibodies. The results indicate that measles-specific cytotoxicity by peripheral lymphoid cells from all three groups of donors is mediated by K cells. It is probable that specificity is provided by a small amount of contaminating serum antibody or immune complexes.

Antibodies, Viral↗