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Biomedical subjects

R H Bonneau

Publications and source records attributed to R H Bonneau.

14 recordsLinked to original sources
PubMed1992

Decreased herpes simplex viral immunity and enhanced pathogenesis following stressor administration in mice.

Mild electric footshock stress was delivered during the dark portion of a 12:12 h light:dark cycle to C57BL/6 female mice that were infected with herpes simplex virus-type 1 (HSV). The studies were designed to correlate viral titer with both humoral and cell-mediated immune responses to HSV infection. Footshock was observed to result in decreased HSV-specific immunity. The numbers of leukocytes in spleens and draining popliteal lymph nodes of footshocked mice were depressed compared to both apparatus control and home cage control mice. A significant suppression of the HSV-specific cytotoxic T lymphocyte (CTL) response was observed in both the spleen and popliteal lymph nodes of footshocked mice. Serum IgM anti-HSV antibody titers were also depressed in footshocked mice. These changes were shown to be correlated with significantly increased viral titers in footshocked mice compared to control mice. These data demonstrate that administration of a relatively mild stressor is associated with depressed HSV-specific cellular and humoral immunity and is associated with increased pathogenicity.

Animals↗
PubMed1991

CD4-positive T lymphocytes are required for the generation of the primary but not the secondary CD8-positive cytolytic T lymphocyte response to herpes simplex virus in C57BL/6 mice.

To understand the cellular basis for recovery from HSV infection, it is critical to identify functional interactions between HSV-specific T lymphocyte subpopulations involved in the generation of the optimal response. To this end, the requirement for CD4+ (L3T4+) T lymphocytes in the development of the primary and secondary CD8+ (Lyt-2+) cytolytic T lymphocyte (CTL) response following HSV infection in C57BL/6 mice was investigated. It was found that chronic depletion of CD4+ cells in vivo by treatment with the mAb GK1.5, which resulted in greater than 95% depletion of peripheral CD4+ T lymphocytes in treated animals, caused a profound decrease in the levels of cytolytic activity obtained during the primary response in the draining popliteal lymph nodes of mice responding to infection in the hind footpads. However, treatment did not affect the levels of in vivo secondary CTL activity in the popliteal lymph nodes, nor the in vitro secondary response in the spleen. The decreased CTL activity observed during the primary response was not due to an inability to prime HSV-specific CTL precursors (CTLp), as full cytolytic activity was obtained following culture of lymphocytes in the presence of exogenous IL-2 and antigen, and the response could be reconstituted by treatment with recombinant IL-2 in vivo. Analysis of the secondary CTL response in the spleen indicated that CD4+ cells were not required for either the generation or maintenance of this aspect of the response. However, blockade of IL-2 utilization by CTL using anti-IL-2R antibodies indicated that this lymphokine was absolutely essential for secondary CTL expansion in vitro. Finally, mice that had been infected 12 months previously exhibited a decreased ability to generate secondary HSV-specific CTL in vitro following CD4-depletion in vivo. Taken together, these results suggest two distinct stages of CTL development during the response: an early primary stage dependent upon the presence of CD4+ cells, and a later, CD4-independent stage operative during the secondary response, which decays with time postinfection.

Animals↗
PubMed1991

Restraint stress differentially affects anti-viral cellular and humoral immune responses in mice.

Physical restraint administered to C57BL/6 mice significantly altered the inflammatory response to influenza virus infection and depressed anti-viral cellular immunity. Restraint-stressed animals showed a pattern of reduced mononuclear cell infiltration and lung consolidation which coincided with elevated plasma corticosterone levels. Furthermore, cellular immunity to virus was significantly depressed; interleukin-2 secretion was reduced by 96% and 59% in the mediastinal lymph nodes and spleens, respectively, as compared to a non-restrained group. However, the magnitude of the humoral immune response to influenza virus was unaffected by restraint stress. Anti-viral IgG antibody levels in restrained/infected mice did not differ when compared to a non-restrained/infected control group 14 days post-infection.

Animals↗
PubMed1991

Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection.

Stressful events suppress a broad spectrum of both humoral and cellular immunological responses. However, studies of the effects of stress on the development of specific antiviral immune responses have not been reported. We have utilized an established murine model of an acute, local footpad Herpes simplex virus type 1 (HSV-1) infection to study the effect of restraint stress on the generation of HSV-specific cytotoxic T lymphocytes (CTL) and natural killer (NK) cell activity. Lymphoproliferative responses in the popliteal lymph nodes following footpad infection as well as the generation of HSV-specific CTL and NK cell activity were depressed in restrained mice compared to infected, unrestrained controls. Frequency analyses of HSV-specific pre-CTL indicated that suppression of the CTL response occurred early in the sequence of events that precedes the generation of functionally lytic CTL and was not mediated by a diminished IL-2 response. Although restrained mice exhibited fewer lymphocytes in the popliteal lymph nodes, the subset distribution was the same as that in the unrestrained controls. Furthermore, stress-induced immunosuppression resulted in a higher titer of infectious HSV at the site of infection. Overall, these findings provide evidence that physiological changes associated with restraint stress can influence the immune response to a specific viral infection and alter the course of viral pathogenesis.

Animals↗
PubMed1991

Stress-induced effects on cell-mediated innate and adaptive memory components of the murine immune response to herpes simplex virus infection.

Using a murine model, we have previously shown that restraint stress is able to suppress the development of herpes simplex virus (HSV)-specific cytotoxic T lymphocytes (CTL) and natural killer (NK) cell activity in the popliteal lymph nodes following local footpad infection. These studies of the primary cell-mediated immune response to HSV infection have been extended to examine the effects of a similar stressor on the development of HSV-specific memory CTL (CTLm) following local and systemic HSV infection. In addition, the effect of stress on HSV-specific CTLm localization and proliferation in the popliteal lymph node following reexposure to HSV was investigated. Lastly, the ability to stimulate HSV-specific CTLm to the lytic phenotype under conditions of restraint stress was examined. Restraint stress did not inhibit the generation of HSV-specific CTLm. However, restraint stress inhibited the ability to activate CTLm to the lytic phenotype. In HSV seropositive mice (primed prior to stress), restraint stress prevented the in vivo activation and/or migration of HSV-specific CTLm in the popliteal lymph nodes. These findings demonstrate that activation of HSV-specific immunological memory can be inhibited by physiological changes associated with stress. Such immune inhibition may provide a possible mechanism for the development of recrudescent herpetic disease.

Animals↗
PubMed1991

The effect of restraint stress on the kinetics, magnitude, and isotype of the humoral immune response to influenza virus infection.

The stress of physical restraint has been shown to modulate the cellular immune response during a viral infection. We have studied the effects of stress on the humoral immune response during infection by influenza virus. Restraint stress altered the kinetics of the antibody response; seroconversion in the IgG and IgA isotypes was delayed in virus-infected C57BL/6 mice subjected to repeated cycles of physical restraint. However, the magnitude and isotype of the mature antibody response were unaffected during the plateau phase; no significant differences were observed between restrained/infected and nonrestrained/infected mice. Thus, the time during infection at which the antibody response was measured was a significant variable in the study of stress-induced alterations of the host's response to a replicating viral antigen. While restraint stress did not significantly affect the magnitude or class of the humoral response, it did alter the kinetics of response.

Animals↗
PubMed1990

Psychological stress-induced modulation of interleukin 2 receptor gene expression and interleukin 2 production in peripheral blood leukocytes.

We explored the expression of the interleukin 2 receptor (IL-2R) and the synthesis of IL-2R messenger RNA by peripheral blood leukocytes obtained from medical students experiencing examination stress in three independent studies. The peripheral blood leukocytes obtained at low-stress baseline periods had significantly higher percentages of IL-2R-positive cells when compared with cells obtained from the same individuals during examinations. In addition, IL2-R messenger RNA in peripheral blood leukocytes decreased significantly during examination periods in a subset of 13 subjects. In one study, we found an increase in the accumulation of interleukin 2 in cultures of cells showing down regulation of IL-2R expression and IL-2R messenger RNA levels. While there are ample data demonstrating stress-associated decrements in the immune response in humans and animals, these data provide the first evidence that this interaction may be observed at the level of gene expression. The data suggest one mechanism whereby the central nervous system modulates the immune response during psychological stress.

Adult↗
PubMed1990

Herpes simplex virus-specific cytolytic T lymphocytes restricted to a normally low responder H-2 allele are protective in vivo.

The herpes simplex virus (HSV)-specific cytolytic T lymphocyte (CTL) response in C57BL/6 (B6, H-2b) mice is restricted exclusively to the class I major histocompatibility complex (MHC) glycoprotein H-2Kb, with no detectable response restricted by H-2Db. However, analysis of the memory CTL population derived from B10.A(2R) (Kk Db) mice indicated that Db was a functional restriction element, and that failure to detect this subpopulation in B6 mice was not caused by the inability of HSV-derived antigens to associate with this self protein. Two long-term polyclonal CTL lines, one generated from B6 mice restricted by Kb and a second generated from 2R mice restricted by Db, were greater than 99% CD8+ and exhibited no natural killer (NK) cell activity. The adoptive transfer of either CTL line to naive recipients prior to infection in the hind footpads with HSV resulted in reduced levels of virus recovered from footpad tissue during the acute phase of infection and a reduction in latent HSV able to be reactivated from the sensory dorsal root ganglia (DRG) during the latent phase of infection. These results demonstrated not only that HSV antigen(s) may associate with Db, allowing restricted recognition controlled by this H-2 gene product, but also that functional Db-restricted CTL have the potential to exert biological activity in an environment in which they are not normally generated.

Alleles↗
PubMed1989

Modulation of acute and latent herpes simplex virus infection in C57BL/6 mice by adoptive transfer of immune lymphocytes with cytolytic activity.

The ability of highly lytic herpes simplex virus (HSV) cytolytic T lymphocytes to modulate the interaction between the murine host (adult C57BL/6 [H-2b] mice) and HSV type 1 Patton resulting in acute infection in the footpad and latent infection in the sensory lumbosacral dorsal root ganglia (L6, L5, L4, and L3) innervating the footpad was investigated. Results indicated that a critical threshold level of infectious HSV was required to establish infection. The adoptive transfer of cytolytic T lymphocytes derived from in vitro cultures after restimulation with HSV-infected, syngeneic stimulator cells exhibiting class I H-2-restricted, L3T4- Lyt-2+ HSV-specific cytolytic activity immediately before infection with a high dose of HSV reduced the levels of infectious HSV recovered from the footpad tissue during acute infection and the levels of latent HSV reactivated from the dorsal root ganglia to levels expected from mice infected with a low dose. Depletion of Lyt-2+ cells from the transferred population abrogated the protective ability, while depletion of L3T4+ cells had little effect. These results suggest that functionally lytic HSV-specific cytolytic T lymphocytes present at the time of HSV infection have the potential to participate in the control of the acute infection and in the subsequent establishment of latent infection.

Animals↗
PubMedDate not supplied

Stress-induced modulation of the immune response to recombinant hepatitis B vaccine.

Each of a series of three hepatitis B (Hep B) inoculations was given to 48 second-year medical students on the 3rd day of a 3-day examination series to study the effect of academic stress on the ability to generate an immune response to a primary antigen. Those students who seroconverted after the first injection (25%) were significantly less stressed and anxious than those who did not seroconvert at that time. In addition, students who reported greater social support demonstrated a stronger immune response to the vaccine at the time of the third inoculation, as measured by antibody titers to Hep B surface antigen (HBsAg) and the blastogenic response to a HBsAg peptide (SAg).

Adult↗