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R C Gehrz

Publications and source records attributed to R C Gehrz.

At least 37 records · Page 2Linked to original sources
PubMed1986

Dw subtypes of serologically defined DR-DQ specificities restrict recognition of cytomegalovirus.

We have investigated the relationship between serologically defined (Ia) and T lymphocyte-defined (LD/Dw) determinants in restricted recognition of cytomegalovirus (CMV) by human T lymphocytes. T lymphocytes isolated from CMV seropositive individuals expressing DQw3/DR4/Dw4 antigens were "sensitized" to CMV in vitro; CMV-specific blasts were isolated and tested for their ability to recognize CMV presented by cells expressing different DR4-associated Dw antigens (i.e., Dw4, Dw10, Dw13, Dw14, and Dw15). Similar studies were also performed using T lymphocytes from individuals expressing DQw1/DR2/Dw2 specificities and antigen presenting cells (APC) expressing the DR2-associated Dw/LD subtypes, Dw2, Dw12, and LD-MN2. CMV-specific T cell blasts were used as responding cells in order to reduce nonspecific background alloresponses which occur with allogeneic APC. In all cases it was found that the determinants involved in restricted recognition of CMV were subtypic to the DR-associated Ia specificities. To distinguish whether Dw specificities associated with DQ or with DR molecules, or both, were involved in these responses, we used anti-DR (L243) and an anti-DQwl (S3/4) monoclonal antibodies (MoAb) to block CMV-specific responses. Both MoAb significantly blocked responses, suggesting that determinants associated with both DR and DQ molecules are involved in restricted recognition of CMV by T cells.

Antibodies, Monoclonal↗
PubMed1986

Varicella-zoster-specific immune responses in acute herpes zoster during a placebo-controlled trial of oral acyclovir therapy.

During a placebo-controlled trial of oral acyclovir therapy for acute zoster in immunocompetent patients, we examined the blastogenic response of peripheral blood mononuclear cells and antibody titers in both placebo and acyclovir recipients to determine whether the drug affected the cell-mediated or humoral immune responses. Proliferative responses to mitogens and two dilutions of varicella-zoster virus antigen were not inhibited when fresh peripheral blood mononuclear cells were simultaneously tested in autologous sera collected before and on day 7 of a 10-day course of 2 g/day of oral acyclovir (plasma drug levels averaged 4.6 microM). Using cryopreserved cells from study days 0, 3, 7, 14, and 30, thawed and tested simultaneously, there was no significant difference at the p less than or equal to 0.05 level between the net proliferative responses at each time point for the two groups. On day 14, however, the proliferative response of the acyclovir group was approximately 50% lower than that of the placebo group. Geometric mean antibody titer rises to varicella-zoster virus were also lower among drug recipients but not significantly so. Although this dose of acyclovir did not have a statistically significant effect on lymphocyte proliferative responses to varicella-zoster virus antigen or antibody titers, the lower values in drug recipients may be a reflection of the ability of acyclovir to terminate viral replication, thus reducing the patient's antigenic burden.

Acyclovir↗
PubMed1985

Cytomegalovirus (CMV)-specific lysis of CMV-infected target cells can be mediated by both NK-like and virus-specific cytotoxic T lymphocytes.

The host response to cytomegalovirus (CMV) involves both humoral and cell-mediated immunity. Because virus-specific cytotoxicity appears to be associated with recovery from CMV infection, we have investigated spontaneous (NK) and cytotoxic T cell (Tc) activity against CMV-infected target cells in normal donors and infants with active CMV infection. Fresh mononuclear cells from seropositive donors expressed low-level, non-MHC-restricted cytotoxic activity that preferentially lysed CMV-infected but not uninfected autologous and allogeneic fibroblasts. No cytotoxic activity was observed when mononuclear cells from seronegative donors were studied. Mononuclear cells from infants with active CMV infection and mononuclear cells from seropositive adults that were pre-incubated with cell-free CMV antigen in bulk culture for 6 days had enhanced cytotoxic activity against CMV-infected target cells sharing one or more class I MHC determinants with the effector cell populations. Selective enrichment or depletion experiments were performed to characterize the effector cell populations involved in the augmented cytotoxic response following in vitro induction with CMV antigen. Purified E-rosette-forming cells expressed increased cytotoxic activity against both virus-infected fibroblasts and the NK target cell, K562. Depletion experiments with monoclonal antibodies and complement indicated that the CMV-specific cytotoxic response involves both an E-rosette-positive, T8+, M1- T-cell subset that most likely represents CMV-specific Tc, and an NK population that can be induced to differentiate by in vitro stimulation with CMV antigen following quantitative NK-cell depletion with monoclonal antibody, B73.1.

Adult↗
PubMed1985

Cytomegalovirus (CMV): specific lymphokine production in congenital CMV infection.

The studies reported here were designed to examine cytomegalovirus (CMV)-specific lymphokine production in infants with congenital CMV infection to elucidate the role of the efferent limb of the immune response to this virus. Mononuclear cells (MNC) from adult control donors and congenitally infected infants were stimulated with mitogen (PHA) or antigens (CMV, mumps), and the supernatants were assayed for production of migration inhibitory factor (MIF) and interferon (IFN). Concordance was observed between lymphocyte proliferative responses to CMV antigen and production of MIF in both control donors and congenitally infected infants. PHA-stimulated cultures from both controls and patients resulted in immune-specific IFN-gamma production in all cases. CMV-stimulated MNC from controls produced IFN when lymphocyte proliferation responses to the antigen were present, whereas those with absent proliferation did not produce IFN. CMV-induced IFN was detected in several patients who had reduced lymphocyte proliferative responses to CMV. The predominant species of IFN stimulated by CMV was neutralized by anti-IFN-gamma, suggesting that CMV induced primarily immune-specific IFN-gamma. In some cases, IFN activity was also reduced to a lesser degree by anti-IFN-alpha, suggesting either the presence of IFN-alpha or of cross-reacting antigenic determinants shared by the two species of IFN. Mumps viral antigen induced primarily IFN-alpha regardless of the immunological status of the donor. We conclude that lymphokine production in congenital CMV reflects the state of activation and/or proliferation of CMV-specific T helper cells rather than an intrinsic defect in the efferent limb of the immune response.

Adult↗
PubMed1984

Two mechanisms of inhibition of human lymphocyte proliferation by soluble yeast mannan polysaccharide.

The literature on chronic mucocutaneous candidiasis contains multiple reports which suggest that loss of cell-mediated immunity in this disease may be related in part to the presence of an inhibitory factor(s) present in patient plasma. One such inhibitory factor has been suggested to be mannan polysaccharide released from the cell wall of the pathogen. The present report describes results of experiments to consider mechanisms by which yeast mannan influences proliferative responses of human lymphocytes. Mannan for these experiments was isolated from Saccharomyces cerevisiae. We observed that mannan-mediated inhibition of proliferative responses to a battery of stimuli (phytohemagglutinin, pokeweed mitogen, and Candida, mumps, streptococcus, cytomegalovirus, and herpes simplex virus antigens) was related in part to an effect of copper associated with the mannan and possibly to the superoxide dismutase activity of the mannan-copper complex. Mannan made deficient in copper by use of a copper-chelating resin appeared to inhibit only lymphoproliferation stimulated by the Candida antigen. These results suggest that inhibitory effects of yeast mannans on lymphoproliferative responses may involve at least two mechanisms, one related to hydrogen peroxide production augmented by mannan-copper complexes and another related to still unknown effects independent of the metal ligand. We propose that our results represent a significant novel observation which may be useful in understanding mechanisms of immunoinhibitory effects of C. albicans mannan.

Copper↗
PubMed1983

Bacterial tracheitis.

During a two-year period, 17 children were brought to the St Paul Children's Hospital with the clinical features of croup, unresponsive to conventional therapy; 12 of these were seen during a two-month outbreak of parainfluenza virus type 1 that occurred in the community. Bronchoscopy showed copious purulent tracheal secretions. Cultures of transbronchoscopic aspirates were positive for bacterial organisms, the most common being Staphylococcus aureus (six of 17) and alpha-hemolytic Streptococcus (seven of 17). Four of these children, all treated conservatively with observation and/or endotracheal intubation, suffered a cardiorespiratory arrest, and two of them died. In contrast, one of 13 children who underwent tracheostomy died. Bacterial tracheitis clinically resembles viral croup, but carries a significant morbidity and mortality. Bronchoscopy documenting the presence of copious endotracheal pus and prompt tracheostomy may reduce the complications of this disease.

Bronchoscopy↗
PubMed1982

Cytomegalovirus infection in infancy: virological and immunological studies.

Immunological and virological studies on 18 infants with cytomegalovirus (CMV) infection were performed. Eleven of these infants were studied on multiple occasions over a period of 1 year. The patients were divided into three clinical groups based on the probable time of infection and the resulting variation in clinical presentation. General parameters of cell-mediated immunity as determined by E-rosette formation and lymphocyte proliferative responses to mitogens and antigens were found to be normal. Quantitation of CMV excretion in urine, CMV-specific immunofluorescent (IF) and complement-fixing (CF) antibody titres and CMV-specific cell-mediated immune responses were done on all patients at approximately monthly intervals. Throughout the study period all patients continued to excrete CMV despite the presence of high antibody titres to the virus. CMV-specific lymphocyte proliferative responses were absent or diminished in 15 of the 18 patients. The immunological and virological status of all patients was similar regardless of the clinical manifestation of infection.

Antibodies, Viral↗
PubMed1981

A longitudinal analysis of lymphocyte proliferative responses to mitogens and antigens during human pregnancy.

T-cell number and mitogen- and antigen-induced lymphocyte proliferative were assessed longitudinally in 18 normal human pregnancies to examine the effects of pregnancy on cellular immunity. The T-cell percentage and mitogen-induced responses did not change significantly in pregnant women as compared to nonpregnant, non-postpartum control adults. However, cell-mediated immune responses to three antigens were dramatically depressed during the third trimester and then returned to early pregnancy levels by 90 days post partum. This reduction in antigen-specific cellular immunity may be necessary to prevent rejection of the histoincompatible fetus by the mother and at the same time may render women in late gestation more susceptible to infection.

Female↗
PubMed1981

Bacterial tracheitis.

Bacterial tracheitis is a recently described clinical entity characterized by high fever, stridor, and airway obstruction. Laryngoscopy shows membraneous inflammation with notable subglottic edema and copious mucopus in the trachea. Staphylococcus aureus is the most common bacterium to be cultured. Subglottic narrowing can be seen on lateral soft-tissue roentgenograms of the neck. Bacterial tracheitis should be treated by establishing a controlled airway by endotracheal intubation or tracheotomy, rather than by usual modalities used for the treatment of croup. Bacterial tracheitis seems to be similar to croup but is more likely to be fatal. Two of the five patients described herein died.

Child↗
PubMed1981

Cytomegalovirus-specific humoral and cellular immune responses in human pregnancy.

Cytomegalovirus (CMV)-specific humoral and cellular immunity was evaluated prospectively during and after 19 normal human pregnancies. Seropositive pregnant subjects had lymphocyte proliferative responses to purified CMV antigen that were markedly depressed by the end of the third trimester of pregnancy despite persistent levels of complement-fixing and immunofluorescent antibodies to CMV. These reduced lymphocyte proliferative responses returned to levels detected early in pregnancy by one year after delivery. None of the subjects excreted CMV during the study period. General parameters of cellular immunity, including thymus derived-cell counts as determined by formation of erythrocyte rosettes and mitogen-induced lymphocyte proliferation, were unaffected. Reactivation of latent CMV during pregnancy might be related to transient depression of CMV-specific cellular immunity.

Antibodies, Viral↗