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Biomedical subjects

S E Starr

Publications and source records attributed to S E Starr.

At least 109 records · Page 6Linked to original sources

Impaired cellular immunity to cytomegalovirus in congenitally infected children and their mothers.

Cell-mediated immunity to cytomegalovirus (CMV) was determined in congenitally infected children and their mothers by use of assays for CMV-specific lymphocyte blastogenesis and interferon production. Six viruric children responded poorly in both assays. Two older nonviruric children responded in the blastogenesis assay, and lymphocytes from one of them produced interferon. Mothers of older children usually responded in the blastogenesis assay, but only one of them produced interferon. Mothers whose infected infants were younger than nine months of age responded poorly in both assays, while control seropositive postpartum women generally responded normally. The cell-mediated immune defects detected in this study may play a role in the pathogenesis of congenital CMV infection.

Cytomegalovirus↗

Live cytomegalovirus vaccination of renal transplant candidates. A preliminary trial.

Significant morbidity and mortality are associated with primary cytomegalovirus infections in renal-transplant recipients. In the hope that immunity to cytomegalovirus could safely be established before transplantation, we vaccinated 12 seronegative renal-transplant candidates with the Towne 125 strain of live human cytomegalovirus. Before transplantation, there were no significant reactions except for erythema and induration at the site of inoculation. All vaccinees seroconverted, and the three patients tested acquired a cytomegalovirus-specific cellular immune response. Ten vaccinees underwent transplantation: Nine have completed at least 3 months of follow-up, and eight retain functioning allografts up to 1 year later. Although cytomegalovirus was isolated from six patients after transplantation, the restriction endonuclease patterns of the viral DNA of four of these isolates differed significantly from those of the vaccine strain. Therefore, it appears that the vaccine strain did not become latent in the host, at least in a form that could be reactivated.

Cytomegalovirus↗

Human neonatal and maternal monocyte-macrophage and lymphocyte-mediated antibody-dependent cytotoxicity to cells infected with herpes simplex.

We recently have described destruction of cells infected with herpes simplex virus by the combination of specific antibody and either lymphocytes or monocyte-macrophages. Because of the role of these cells in viral immunity and the severity of HSV in neonates and pregnant women, cord blood from 11 healthy neonates and peripheral blood from seven of their postpartum mothers were analyzed for MP and lymphocyte antibody-dependent cellular cytotoxicity against cells infected with HSV. Cord blood yielded more lymphocytes and maternal blood fewer lymphocytes than did blood from adult female control subjects. Baseline cytotoxicity of cord MP and lymphocytes and maternal lymphocytes was significantly lower than control values. There was no significant difference in MP or lymphocyte ADCC, although maternal ADCC tended to be lower than that of control subjects. Analysis of cord plasma indicated that antibody able to participate in lymphocyte and MP ADCC crosses the placenta. These data demonstrate intact ADCC but possible defects in baseline cytotoxicity with leukocytes obtained from neonates and pregnant women. Further consideration of the use of HSV antibody for prevention and therapy of neonatal HSV infection is suggested.

Antibodies, Viral↗

Role of T lymphocytes in recovery from murine cytomegalovirus infection.

Congenitally athymic nude (Nu/Nu) mice inoculated intraperitoneally with murine cytomegalovirus (MCMV), in doses as low as 1.3 X 10(1) plaque-forming units succumbed to the infection. In contrast, the mean lethal dose for heteroxygous euthymic (Nu/+) littermates was 4 X 10(3) plaque-forming units. Though histopathological changes consistent with MCMV infection were found in the spleen, lungs, and adrenals of nude mice, there were only small focal areas of involvement in the liver. In contrast, Nu/+ mice dying from infection had pathological evidence of severe hepatitis. Spleen cells from immune and control BALB/c mice were injected intravenously into syngeneic mice that had been inoculated previously with lethal doses of MCMV intraperitoneally. Mice receiving 1 X 10(7) or more immune spleen cells were protected against the infection, whereas mice receiving 1 X 10(8) control spleen cells or immune serum were not. Treatment of immune spleen cells with anti-theta serum and complement significantly reduced their protective effect. Immune mechanisms associated with T lymphocytes appear to be critical for recovery from MCMV infection.

Animals↗

Human monocyte-macrophage-mediated antibody-dependent cytotoxicity to herpes simplex virus-infected cells.

Human peripheral blood mononuclear cells which mediate antibody-dependent cellular cytotoxicity (ADCC) against herpes simplex virus- (HSV) infected target cells consist of both adherent (MA) and nonadherent (MNA) effector cell populations. These two cell populations can be distinguished by their different phagocytic properties and morphologic appearance, their requirement for antibody in the ADCC reaction, and the rapidity with which they lyse target cells in the presence of immune serum. The MA cells are predominantly phagocytic and have the morphologic characteristics of monocyte-macrophages, whereas the MNA cells are nonphagocytic and appear to be small to medium-sized lymphocytes. Optimal expression of ADCC by MA cells requires higher concentrations of immune serum than does MNA cell-mediated ADCC. MA-mediated cell killing is first detectable by 8 hr and reaches completion after 24 hr of incubation. In contrast, MNA-mediated ADCC produces target cell damage by 2 hr and reaches completion at 8 hr of incubation. Unlike MNA effector cells, the MA effector cells are profoundly inhibited after preincubation with either latex or silica particles. The HSV immune status of the donor had no effect on the ability of either cell population to mediate ADCC. These data demonstrate the participation of both nonadherent mononuclear cells, presumably K cells, and monocyte-macrophages, in ADCC directed against HSV-infected target cells.

Antibodies↗

Human polymorphonuclear leucocytes as mediators of antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.

Human polymorphonuclear leucocytes (PML) were able to mediate antibody-dependent cellular cytotoxicity (ADCC) against target cells acutely infected with type 1 Herpes simplex virus. The reaction mediated by PML occurred more slowly and required higher concentrations of immune serum than that mediated by human mononuclear cells (MC). At the same ratio of effector cells to target cells, PML-mediated ADCC was less than MC-mediated ADCC. The observed relationship between the number of effector cells added, and the number of target cells lysed, showed that cytolysis mediated by both PML and MC was consistent with 'one hit' probability predictions. This suggested that target cell death resulted from an interaction with a single effector cell. The calculated frequency of effector cells in PML preparation was similar to that in MC, approximately 3-5%. Preliminary examination of the nature of the effector cells suggested that they did not comprise a morphologically distinct subclass of PML. These experiments demonstrate a possible new role for PML in host defence against viral infections.

Antibodies, Viral↗

Effects of immunostimulants on resistance of newborn mice to herpes simplex type 2 infection.

Since age-dependent diminished macrophage function has been related to the increased susceptibility of newborn mice to herpes simplex virus (HSV) infection, the effect of several agents which might activate macrophages or other cells involved in immunity was investigated. BCG, typhoid vaccine, brucella vaccine, levamisole, or staphage lysate were administered to newborn mice prior to challenge with HSV-2. Of these agents, only BCG, administered ip or id 6 days prior to challenge, was found to increase the survival rate of newborn mice. The possible use of BCG, alone or in combination with other modalities, for the prevention or treatment of neonatal HSV infections is discussed.

Animals↗

Immunology of herpes simplex virus infection: relevance to herpes simplex virus vaccines and cervical cancer.

The immunology of herpes simplex infections has been reviewed, particularly in relation to potential herpes simplex virus (HSV) vaccines, and to the association between HSV and cervical cancer. Relevant data from humans, experimental animals, and in vitro systems implicate both specific immune mechanisms and nonspecific factors in the course of HSV infections. There appear to be complex interactions between the various populations of mononuclear cells, marcrophages, and lymphokines or other humoral factors. It is not yet possible, however, to pinpoint the crucial factors determining the different manifestations of the viral infection (primary infection, endogenous recurrence, or exogenous reinfection) in the various human hosts, although genetic factors may be important. While numerous animal models of HSV infection are available for the evaluation of HSV vaccines, models of HSV-induced cervical cancer require further exploration.

Age Factors↗

Stimulation of human lymphocytes by Herpes simplex virus antigens.

Lymphocytes from individuals with laboratory evidence of prior infection with herpes simplex virus (HSV) type 1 or type 2 demonstrated transformation (av antigens. Higher stimulation indexes were obtained when lymphocytes were incubated with the homologous as compared with the heterologous antigen. Higher mean lymphocyte stimulation indexes were also demonstrated in seropositive as compared with seronegative individuals. Lymphocytes from children with HSV-1 stomatitis usually became responsive to HSV-1 antigen within 2 to 6 weeks after the onset of illness. Lymphocytes from infants with neonatal HSV-2 infection were stimulated by HSV-2 antigen.

Antibodies, Viral↗