Elinor M. Levy

Short-term immunological effects of induced emotion

&NA; Twenty healthy volunteers (half male) recalled and relived maximally disturbing (NEG) and maximally pleasurable (POS) emotional experiences. Forty minutes of silence, then neutral conversation, preceded and followed 40 minutes of emotion elicitation (NEG and POS randomly rotated). They were under video, cardiovascular, and immunological monitoring. Subjects reported appropriate emotions and showed significant cardiovascular activation during the NEG condition. Speech alone had an independent cardiovascular activating effect. Emotion, particularly NEG, led to further activation. NEG emotion promoted significant declines in mitogenic lymphocyte reactivity, followed by return to pre‐emotion levels. A similar though less extreme decline was seen in the POS condition. There was a weak trend for elevated natural killer cell activity under the NEG condition, possibly due in part to changed trafficking patterns. Correlational findings confirmed these group effects. The decline in mitogenic reactivity during POS emotion appeared to be due to subtle degrees of tension and excitement triggered by the experimental experience regardless of the exact emotions recalled. Results suggest that immunologic processes are sensitive to influence by arousal of emotion.

Immunosuppression in mice induced by cold water stress.

A number of studies indicate that stress can result in suppression of the immune system in animals and man. Most of the studies have focused on alterations of lymphocyte function while only a few have investigated alterations of macrophage function or macrophage cytokine production. Macrophages play an essential role in homeostasis of the immune response. Indeed, the earliest events of the immune response occur in cells of the monocytic lineage, and their secretion of various cytokines may have both immunological and nonimmunological effects. The present studies were undertaken to determine whether alterations in macrophage physiology occur in mice subjected to a stress stimulus. Our studies in mice exposed to cold water stress for 4 days indicated reduced numbers of thymocytes and splenocytes, decreased T-cell blastogenesis, and reduced NK activity. Examination of elicited peritoneal macrophages from stressed mice revealed increased prostaglandin E2 (PGE2) secretion and decreased immune region associated antigen (Ia) expression in response to interferon-gamma. Despite elevated PGE2 levels, indomethacin was generally unable to restore depressed immune function. Of special interest was the finding that cell-associated and secreted interleukin 1 were significantly higher from unstimulated elicited macrophages from stressed mice. These results suggest that early in the response to stress, functions of a variety of cells within the immune system, especially macrophages, are altered and that dysregulated macrophage function may well contribute to the generalized suppression of the immune response in cold water stressed mice.

Changes in mitogen responsiveness lymphocyte subsets after traumatic injury: relation to development of sepsis.

Head injury and multiple trauma patients were evaluated for mitogen responsiveness and lymphocyte subset frequencies within the first few days after injury. The profile obtained was compared to the patients clinical course to see if there was a relation between early immune abnormalities and the subsequent development of unanticipated sepsis. Lymphocytes from multiple trauma patients were generally hyporesponsive to in vitro stimulation with a suboptimal dose of the mitogen phytohemagglutinin (PHA). In contrast, the response of head injured patients was comparable to that of the control group. There was a significant decrease in the relative number of multiple trauma patients T4 (29.3 vs 48.6%) and T11 (48.9 vs 74.7%) positive populations (P less than 0.01). There was no change in the percentage of T8-positive cells (19.0 vs 20.5%). Patients with head injuries also had a decrease in T4-positive cells (35.9%). The percentage of cells with B cell and natural killer (NK) markers remained normal. Thus trauma patients appeared to have an increase in null cells. Six patients whose PHA responses were among the lowest developed sepsis early after trauma. The changes in subset distributions although possibly contributing to a decreased responsiveness did not predict the ability to respond to PHA or the development of sepsis.

Inhibition of an in vitro antibody response by a suppressor cell in normal bone marrow

Abstract Murine bone marrow cells can suppress the in vitro primary antibody response of normal spleen cells without apparent cytotoxicity. The bone marrow cells suppress the response to both T-dependent (SRBC) and T-independent (DNP-Ficoll) antigens. When bone marrow cells are fractionated on a sucrose density gradient, the suppressive activity is found in the residue rather than the lymphocyte fraction. The suppressive activity is either unaffected or enhanced by treatment with anti-T- and anti-B-cell serums. Pretreatment of mice with phenylhydrazine which reduces the number of pre-B cells did not reduce the suppressive activity of their bone marrow cells. Suppressive activity is abolished by irradiation of the marrow cells in vitro with 1000 R prior to assay. The activity is present in the marrow of thymus deficient (nude) mice, infant mice, and mice which have been made polycythemic by transfusion. Furthermore, the suppressor cell can phagocytize iron carbonyl particles, is slightly adherent to plastic and Sephadex G-10, and can bind to EA monolayers. We conclude that the suppressor cell is not a mature lymphocyte or granulocyte nor a member of the erythrocytic series, but is likely to be an immature cell possibly of the myeloid series. We speculate on the physiologic role of this cell.

The effect of changes in thiol subcompartments on T-cell colony formation and cell cycle progression: relevance to AIDS.

Recently, it has been shown that intra- and extracellular thiol levels are significantly lower than normal even in the relatively early stages of human immunodeficiency virus (HIV) infection. It is plausible that this deficiency could contribute both to the loss of T-cell function and the ability to replenish T cells associated with HIV infection. We had previously reported that the T-cell colony-forming cell (T-CFC) is impaired in HIV infection and that it can be enhanced with the thiol compounds 2-mercaptoethanol (2-ME) and N-acetylcysteine (NAC). In this study, the effect of the thiol-depleting reagents buthionine sulfoximine, cyclohexene-1-one, and copper phenanthroline on T-CFC formation and cell cycle progression was determined in HIV+ subject and/or controls. All three reagents inhibited T-CFC formation and cell cycle progression with a suggestion that colony formation by cells from HIV+ subjects was more sensitive to the effects of thiol depletion. 2-ME and NAC enhanced effect of NAC did not appear to involve increased protein kinase C translocation. Our results suggest that oxidation of membrane thiols, as well as depletion of intracellular glutathione, inhibits T-CFC formation as well as cell cycle progression for mitogen-stimulated cells in bulk culture.

Elevation of circulating beta-endorphin levels with concomitant depression of immune parameters after traumatic injury.

Immunosuppression is frequently observed after traumatic injury, and is associated with the subsequent development of sepsis. Although a number of factors such as age, nutritional status, and the degree of injury have been related to the severity of the immunosuppression that occurs, the physiologic alterations leading to immunosuppression are not well defined. We hypothesized that changes in the endogenous opiate peptides, such as beta-endorphin, might contribute to changes in the immune system following injury. Levels of circulating beta-endorphin, responsiveness to the mitogen PHA, and the frequency of circulating T11, T4, and T8 cells were measured in trauma patients hospitalized in a surgical intensive care unit. beta-endorphin levels were elevated during the first 4 days after trauma (134.1 +/- 22.5 vs. 49.3 +/- 4.3 pg/ml, mean +/- S.E., patient vs. control; p less than 0.001). During the same time period patient PHA response (10,852 +/- 3,775 vs. 28,147 +/- 12,078; p less than 0.05), and the per cent of T4 positive (31.2 +/- 2.6 vs. 47.0 +/- 1.4; p less than 0.001) cells were lower than controls. These parameters were not significantly different from control values when measured at later times. Thus we conclude there is a temporal association of depressed immune parameters and elevated beta-endorphin levels after traumatic injury.

Surface immunoglobulin-positive T lymphocytes in HIV-1 infection: Relationship to CD4+ lymphocyte depletion

T lymphocytes bound to autologous immunoglobulin (surface Ig + T cells) and serum antibodies that bind to allogeneic lymphocytes have been detected in HIV-1-infected individuals, but their significance in the immunopathogenesis of HIV-1 infection is uncertain. We tested peripheral blood from HIV-1-infected individuals to determine if surface Ig+ T cells are specific for HIV-1 infection and are associated with CD4+ lymphocyte depletion. The majority of HIV-1-infected individuals contained substantial numbers of circulating surface Ig+ T cells. The presence of such cells was restricted to seropositive individuals and not related to risk factors associated with the acquisition of HIV-1 infection. Autologous immunoglobulin was detected on both CD4+ and CD8+ cells in all patients tested. Most individuals with surface Ig+ T lymphocytes also had serum anti-T-lymphocyte antibodies. The presence of surface Ig+ T lymphocytes correlated significantly with lower absolute CD4+ lymphocyte counts only in asymptomatic, HIV-1-infected individuals.

Psychological and immunological associations in men with AIDS pursuing a macrobiotic regimen as an alternative therapy: A pilot study

A group of men with AIDS who chose to follow a macrobiotic regimen as an alternative form of therapy was studied for the possible influence of psychological factors on their clinical progression. In this group, men with Kaposis sarcoma (KS) had an estimated survival time of 60% at 3 years. Moreover, there was a tendency for lymphocyte number to increase during the first 3 years following diagnosis with KS. A subset of eight of these men with KS and one man with Pneumocystis carinii pneumonia (PCP) agreed to fill out a battery of psychological questionnaires. The results suggest low levels of fatigue, negative affect, and confusion, but high levels of vigor in this subgroup. Additionally, there was significant positive associations of CD4 positive lymphocyte numbers with trait curiosity and hardiness scores and significant negative associations with anxiety and depression. Mitogen responsiveness followed a similar pattern, but only a positive association with curiosity reached significance. Caution has to be used in interpreting such data, especially in view of the size of the sample and the complexity of the cohort. Nonetheless, these findings clearly suggest the need for prospective studies on the influence of psychological factors on the progression of AIDS.

Defective T-cell differentiation in acquired immune deficiency syndrome (AIDS)

A decline in T-cell lymphocyte number is the central characteristic of acquired immune deficiency syndrome (AIDS). The reason for the loss of these cells is not well understood. We investigated the hypothesis that defects in T-cell differentiation contributed to T-cell loss using anin vitro colony assay that measures T-cell precursor (CFU-T) frequency. The results indicate a substantial generalized decrease in CFU-T in people with AIDS (P<0.01), most of whom have Kaposis sarcoma, and an occasionally severe decrease in CFU-T in people with ARC. Some of the cells from low colony formers suppressed colony formation by control cells. In addition, plasma from people with AIDS was less supportive of colony growth than control plasma. Decreased Ia expression on adherent mononuclear cells did not correlate with colony formation. A defect in T-cell repopulation can help explain the loss of T cells associated with AIDS.

Mitogen induced cellular cytotoxic activity as a monocyte function in human peripheral blood preparations

Abstract The effector cell population in man responsible for mitogen induced cellular cytotoxicity (MICC) of chicken erythrocytes was investigated using several separation techniques, including free flow electrophoresis. Electrophoresis produced substantial monocyte enrichment in some fractions with substantial depletion in others. MICC activity was seen to correlate with monocyte content in these fractions. Furthermore, removal of phagocytic cells with carbonyl iron and removal of adherent cells on plastic petri dishes depleted preparations of MICC activity. Thus it is suggested that under conditions described in this paper, the effector cell of the MICC assay in man appears to be a monocyte. This MICC effector cell was shown to be different from the effector cell in the natural killing (NK cells) of RPMI 6410 cells.