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Biomedical subjects

S Kohl

Publications and source records attributed to S Kohl.

At least 55 records · Page 3Linked to original sources
PubMed1990

Reduced antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells of salivary polymorphonuclear leukocytes and inhibition of peripheral blood polymorphonuclear leukocyte cytotoxicity by saliva.

Blood polymorphonuclear leukocytes (BPMN) have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC) against HSV-infected cells. Although HSV infections are frequently found in the oral cavity, the ADCC capacity of salivary PMN (SPMN) has not been studied, mainly because methods to isolate SPMN were not available. We have recently developed a method to isolate SPMN, and in this study have evaluated their ADCC activity against HSV-infected cells. SPMN were obtained by repeated washings of the oral cavity, and separated from epithelial cells by nylon mesh filtration. ADCC was quantitatively determined by 51Cr release from HSV-infected Chang liver cells. SPMN in the presence of antibody were able to destroy HSV-infected cells, but SPMN were much less effective in mediating ADCC than BPMN (3.4% vs 40.7%, p less than 0.0001). In the presence of antiviral antibody, SPMN were able to adhere to HSV-infected cells, but less so than BPMN (34% vs 67%), and specific antibody-induced adherence was significantly lower in SPMN (p less than 0.04). The spontaneous adherence to HSV-infected cells was higher for SPMN than BPMN. SPMN demonstrated up-regulation of the adhesion glycoprotein CD18, but down-regulation of the FcRIII receptor. Incubation with saliva decreased ADCC capacity of BPMN, up-regulated CD18 expression, and down-regulated FcRIII expression.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Protection against murine neonatal herpes simplex virus infection by lymphokine-treated human leukocytes.

One-week-old mice were protected against a uniformly lethal herpes simplex virus (HSV) infection by IL-2 alone, but especially by the addition of human mononuclear cells (MC) plus IL-2. The dose response of IL-2 was biphasic. The addition of MC from cord blood did not enhance IL-2-mediated survival. Because the effect of IL-2 alone, or IL-2 plus MC, was ablated by anti-IFN-gamma and human neonates have an IFN-gamma production defect, the protective effect of MC plus human IFN-gamma (HuIFN-gamma) was tested. MC from adults cultured for 5 days in HuIFN-gamma afforded protection. At least 1 x 10(6) HuIFN-gamma-treated MC were required with increasing survival to 1 x 10(7) MC. The effector cell activity was ablated by adherence, silica, L-leucine methyl ester treatment or treatment with Leu-M3 plus C (all macrophage markers), and OKT4 plus C treatment (CD4 marker). Use of Leu-11, Leu-7, OKT3, or OKT8 plus C did not inhibit protection and excluded NK or T cell participation. In addition to survival, the ability to produce anti-HSV antibody was reconstituted. For the first time protection was afforded by human cord blood MC after treatment with HuIFN in vitro. We have identified an IFN-gamma-driven protection system against murine neonatal HSV infection mediated by human adult- or cord blood-derived CD4-positive macrophages. Protection is associated with enhanced effector cell function and reconstitution of the neonatal antibody production defect.

Age Factors↗
PubMed1990

Herpes simplex virus type 2 meningoencephalitis resistant to acyclovir in a patient with AIDS.

A case is reported of relapsing fatal meningoencephalitis caused by a neurovirulent thymidine kinase-positive (TK+) type 2 herpes simplex virus (HSV) that developed thymidine kinase deficiency (TK-) during intravenous acyclovir therapy. A patient with AIDS was admitted for acyclovir treatment of a persistent perirectal herpetic ulcer. He subsequently developed meningoencephalitis. A TK+ type 2 HSV was isolated from a brain biopsy specimen. A progressive and fatal relapse occurred, and a TK- type 2 HSV was isolated from his cerebrospinal fluid. Restriction endonuclease analysis of viral DNA from perianal, brain, and cerebrospinal fluid isolates were similar, suggesting that they were the same viral strain. Animal virulence studies indicated significant cutaneous virulence in immunocompromised mice models for the TK- isolates. This case is notable because TK- HSV have, in the past, lacked neurovirulence and because acyclovir resistance developed during therapy and caused the patient's death.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Analysis of the role of antibody-dependent cellular cytotoxic antibody activity in murine neonatal herpes simplex virus infection with antibodies to synthetic peptides of glycoprotein D and monoclonal antibodies to glycoprotein B.

The role of antibody in neonatal herpes simplex virus (HSV) infection remains controversial. A battery of well-characterized monoclonal antibodies to HSV glycoprotein B (gB), and polyclonal antibodies against synthetic peptides of predicted epitopes of HSV glycoprotein D (gD) were used to determine in vitro functional activity and association with protection against lethal infection in a murine model of neonatal HSV disease. Antiviral neutralization activity of HSV was not associated with antibody-dependent cellular cytotoxicity (ADCC) activity to HSV-infected cells in vitro. In a model of high dose challenge (10(4) PFU), protection was not afforded by any antibody alone, but was by antibody plus human mononuclear cells, and highly associated with ADCC functional activity (P less than 0.001). In a low dose challenge model, neutralizing activity of antibody alone was associated with protection in vivo (P less than 0.001). Of the nine neutralizing epitopes of gD in vitro, eight were predicted surface regions. Four of the five epitopic sites of gD (2-21, 267-276, 288-297, and 303-312) that were determined to be important targets of ADCC and in vivo protection were also predicted to be surface regions. The only exception was the antiserum to region 52-61 which was predicted to be buried and also showed these activities. ADCC as well as neutralizing antibody activity are important in protection against neonatal HSV infection.

Animals↗
PubMed1989

Interleukin-2 protects neonatal mice from lethal herpes simplex virus infection: a macrophage-mediated, gamma interferon-induced mechanism.

Administration of human recombinant interleukin-2 (IL-2) protected neonatal mice from a lethal herpes simplex virus (HSV) infection. Protection was not associated with viral antibody production, enhanced natural killer cell cytotoxicity, or intrinsic resistance of macrophages to viral infection. Protection was associated with increased macrophage-mediated antiviral antibody-dependent cellular cytotoxicity (ADCC). Spleen cells from IL-2-treated neonatal mice and from neonatal mice that were treated in vitro with IL-2 transferred protection to neonatal mice. These cells, by adherence, silica, and asialo GM 1 antibody treatment, were shown to be macrophages. IL-2 treatment in vitro enhanced the neonatal macrophages' ADCC function and superoxide release. Similar protection was induced by gamma interferon (IFN-gamma)-treated spleen cells. Antibody to IFN-gamma ablated both IFN-gamma- and IL-2-induced protection by adherent spleen cells. Thus, IL-2-mediated protection against murine neonatal HSV infection was affected by stimulated macrophage activity, via helper T cell-produced IFN-gamma.

Animals↗
PubMed1989

Neonatal antibody-dependent cellular cytotoxic antibody levels are associated with the clinical presentation of neonatal herpes simplex virus infection.

The role of antiviral antibodies in protection against neonatal herpes simplex virus (HSV) infection remains controversial. The relationship between neonatal and maternal anti-HSV antibodies and disease presentation was analyzed in 47 babies. Of the neonates, 77% had localized and 23% had disseminated HSV infection. Antibody-dependent cellular cytotoxic (ADCC) antibodies were evaluated in comparison with HSV neutralizing antibodies. High maternal (greater than 1:10(4)) or neonatal (greater than 1:10(3)) anti-HSV ADCC antibody levels or high neonatal antiviral neutralizing levels (greater than 1:20) were independently associated with an absence of disseminated HSV infection. Cochran-Mantel-Haenszel analysis demonstrated that ADCC levels were associated with disease status (P less than .02) while controlling for the level of neutralizing antibody.

Antibodies, Viral↗
PubMed1989

The neonatal human's immune response to herpes simplex virus infection: a critical review.

The neonate has a variety of quantitative defects in its immune response in elements of both the early containment phase and the later curative phase to HSV infection (Table 2). It is likely that the combination of these defects, and possibly others yet to be delineated (IL-2 response, T cell cytotoxicity response, etc.), account for dissemination or for locally progressive illness in newborn infants. It is unlikely that all these defects can be reconstituted by current available modalities (immunoglobulin, interferons, interleukins). One would hope that improving one or a few of these mechanisms may tilt the balance away from dissemination or central nervous system disease and allow the neonate to mature immunologically.

Antibody Formation↗
PubMed1988

Antibody to cloned HSV glycoproteins B and D plus adult human leukocytes protect neonatal mice from lethal HSV infection.

Antisera produced by HSV infection or following vaccination of guinea pigs with the cloned herpes simplex virus (HSV) glycoproteins gB and gD were compared for in vitro antibody-dependent cellular cytotoxicity (ADCC) activity and for in vivo protection. Antibody from guinea pigs was able to participate in ADCC with human mononuclear cells in vitro, anti-gBgD serum being equivalent to HSV convalescent sera. In vivo, each of the guinea pig sera was able to protect neonatal mice from a fatal HSV-1 infection when given with human mononuclear cells but not when given alone. The anti-gBgD serum was the most effective in vivo, protecting 15 of 17 (88%) neonatal mice when given at a 10(-4) dilution with human mononuclear cells and was the only guinea pig serum protective at a 10(-6) dilution (5 of 7 neonatal mice).

Animals↗
PubMed1988

Defects in interleukin-2 stimulation of neonatal natural killer cytotoxicity to herpes simplex virus-infected cells.

Natural killer cytotoxicity (NKC) is an important early defense mechanism in viral infections. We determined the ability of interleukin-2 (IL-2), an NKC stimulator, to enhance defective neonatal NKC to virus-infected cells. Human recombinant IL-2-stimulated adult and cord blood NKC to herpes simplex virus-infected cells in a time-dependent and dose-dependent fashion. The highest level of neonatal IL-2-stimulated cytotoxicity approached the level of unstimulated cytotoxicity when adult cells are used. Single-cell experiments suggested that the cord blood defect was due not to decreased adherence but to lysis or recycling defects. IL-2 stimulated adhesion in the presence of antibody but had no stimulatory effect on antibody-dependent cellular cytotoxicity. The relative defects in IL-2 stimulation of neonatal NKC suggest that its lone use as a therapeutic or protective agent against herpes simplex virus infections is unlikely to be successful, and may require concomitant adult cells if NKC is a critical mechanism.

Cell Adhesion↗
PubMed1988

Herpes simplex virus encephalitis in children.

Herpes simplex encephalitis (HSE) is an uncommon disease, yet 25 to 30 per cent of cases involve children. The initial clinical findings are nonspecific (fever, altered mental status), but most cases evolve to demonstrate focal neurologic signs and symptoms. The CSF is abnormal in over 90 per cent of cases. The EEG, CT, and MRI will further help in detecting focal encephalitis. The clinician caring for a child with focal encephalitis should institute broad-spectrum antimicrobial therapy plus acyclovir, pending definitive diagnosis by ancillary tests or brain biopsy, which is positive for HSE 33 to 55 per cent of the time and is diagnostic for other treatable conditions 10 to 20 per cent of the time. Acyclovir is the drug of choice for HSE and substantially reduces mortality and morbidity. The management of HSE in a child requires an experienced team of specialists and laboratory support in a tertiary intensive care setting.

Acyclovir↗
PubMed1988

Use of interleukin-2 and macrophages to treat herpes simplex virus infection in neonatal mice.

We have developed a model of therapy for herpes simplex virus (HSV) infection in neonatal mice. Using a lower dose of virus (10(2) plaque-forming units administered intraperitoneally), we have been able to treat infected mice with syngeneic or allogeneic adult mouse macrophages in combination with three doses of human recombinant interleukin-2. Therapy resulted in a 42%-85% survival rate. Although production of antibody to HSV was associated with successful treatment, early administration of antibody did not improve survival.

Animals↗