Interferon: a cytotoxic T lymphocyte differentiation signal

Human T cell clones which were able to proliferate in response to specific stimuli but could not kill even in the presence of lectins were found to acquire the specific lytic function when interferon alpha or gamma was added on day 1 of the 7-day restimulation culture. These results demonstrate that interferon may act as a cytotoxic T lymphocyte differentiation signal. This signal can be blocked by the monoclonal antibody LeoA1 which recognizes a 70-kDa cell surface structure, involved in cytotoxic T lymphocyte differentiation.     

Suppression of thyrotropin in the low-thyroxine state of severe nonthyroidal illness

In a prospective study, we assessed the role of thyrotropin in the development of the low-thyroxine state that is associated with severe illness. We measured the serum thyrotropin and thyroid hormone concentrations longitudinally in 35 patients with hematopoietic cancer or aplastic anemia who were treated by bone-marrow transplantation. In 19 patients thyroxine declined sharply after bone-marrow transplantation and was associated with a reduction of the serum thyrotropin in the 17 patients tested, often to levels below the normal range. The serum triiodothyronine level, free thyroxine index, and free thyroxine level also declined in these patients. In the patients who recovered, clinical improvement was accompanied by the return of thyrotropin and thyroid hormone concentrations to their pretreatment ranges. These and related findings suggest that the low-thyroxine state of severe illness is the result of several events, one of which is failure of the normal negative-feedback control of the pituitary-thyroid axis due to illness-associated, decreased secretion of thyrotropin. The notion that such patients are "euthyroid" must be questioned, but the possible value of thyroid hormone-replacement therapy in these circumstances remains to be determined.     

Adherence of Staphylococcus epidermidis to fibrin-platelet clots in vitro mediated by lipoteichoic acid.

The adherence of two strains of Staphylococcus epidermidis to human fibrin-platelet clots in vitro was investigated. Both strains were noncapsulated, nonhemagglutinating, and nonslime producers. Binding was not related to surface charge, carbohydrate profile, or hydrophobicity of the bacteria. Adherence was reduced four- to sixfold (P less than 0.001) on pretreatment of bacteria with lipase, while neuraminidase, trypsin, phospholipase C, and sodium periodate did not alter their binding. Pretreatment of bacteria with substances known to bind lipoteichoic acid (LTA), such as human albumin and anti-LTA antibodies, also resulted in a fourfold (P less than 0.001) reduction in adherence. Prior incubation of clots with free LTA, but not with deacylated LTA, produced a fourfold (P less than 0.001) decrease in the adherence of homologous and heterologous strains of S. epidermidis. A similar reduction was also observed when LTAs derived from Staphylococcus aureus and Streptococcus pyogenes were used. These data provide evidence that the lipid moiety of LTA has a central role in the adherence of S. epidermidis to fibrin-platelet clots in vitro.     

Stress, coping, and hepatitis B antibody status

OBJECTIVE: The present study investigated the association between exposure to stressful life events, coping style, and antibody status after hepatitis B vaccination. METHODS: Two hundred sixty medical school undergraduates, who had received the three-dose hepatitis B vaccine before recruitment to this study, completed questionnaires measuring exposure to stressful life events during the past year, customary coping strategies, and health behaviors. Antibodies against hepatitis B surface antigen were determined; levels <100 mIU/ml were deemed inadequate. RESULTS: Two participant cohorts were identified: those vaccinated within the last year and those vaccinated earlier. In the early vaccination cohort, participants with greater-than-average stress exposures had a more than two-fold increased risk of having an inadequate antibody titer. Coping by accepting the reality of stressful situations proved protective, whereas coping by substance use increased the risk of having an inadequate antibody count in this cohort. These associations remained significant after adjustment for possible mediators. Furthermore, the effects of stress and coping were largely independent of one another. Neither stress nor coping was significantly associated with antibody status in the recently vaccinated cohort. CONCLUSIONS: The present study confirms that the immune system is sensitive to variations in psychological factors. Stressful life events and coping strategy seem to have a continuing impact on hepatitis B antibody status.     

Dyadic disturbances in cocaine-abusing mothers and their infants

A recently developed instrument for the quantification of mother-infant interaction, the Parent-Child Early Relationship Assessment (PCERA), was used to observe drug-abusing mothers and their infants. Compared to the standardization sample used in the development of the PCERA, these drug-abusing mothers (N = 5) showed a tendency toward rigidity and overcontrol in their parenting, a lack of enjoyment and pleasure in relating to their infants, and limited emotional involvement and responsivity in their interaction. An analysis of the dyadic behaviors showed an overall reduction in reciprocity, mutual enjoyment, and regulation of interaction between mother and infant.     

Fos immunoreactivity in the lamina terminalis of adrenalectomized rats and effects of angiotension II type 1 receptor blockade or deoxycorticosterone

Neural activity, as measured immunohistochemically by the presence of Fos protein, was determined in the lamina terminalis, a thin strip of tissue forming the anterior wall of the third brain ventricle, after adrenalectomy. Several weeks after surgery, the adrenalectomized rats were maintained with access to water and a low sodium diet for five days. In addition, hypertonic (0.5M) NaCl solution was available for the entire five-day period (sodium available) or only during the first four days (sodium unavailable). The number of neurons expressing Fos, determined at the end of the fifth day, was increased in the adrenalectomized rats with or without NaCl solution to drink. Fos activity in the median preoptic nucleus was increased only in adrenalectomized rats without access to NaCl solution. Treatment of adrenalectomized rats with the sodium-retaining mineralocorticoid hormone, deoxycorticosterone, at the end of the fourth day, decreased Fos expression in the subfornical organ and the organum vasculosum of the lamina terminalis when NaCl solution was available but not when the NaCl solution was unavailable. In the adrenalectomized rats with NaCl solution available, mineralocorticoid treatment decreased both urinary sodium excretion and daily sodium intake. Brain nuclei in the lamina terminalis also became activated in intact rats made sodium deplete by treatment with the diuretic, furosemide. Relative to sodium-deplete intact rats, however, sodium-deplete adrenalectomized rats had a greater number of neurons expressing Fos in the organum vasculosum. Treatment of sodium-deplete rats, adrenalectomized or intact, with the angiotensin II-type 1 receptor antagonist, ZD7155, decreased sodium intake and Fos expression in the subfornical organ but not in the organum vasculosum of the lamina terminalis or median preoptic nucleus.In conclusion, the results demonstrated that activation of the brain nuclei located in the lamina terminalis of adrenalectomized rats was primarily related to sodium deficit and not to the absence of the mineralocorticoid hormones, although the adrenal hormones may have a role in limiting the activation of organum vasculosum of the lamina terminalis during sodium depletion. Furthermore, the results obtained with the administration of the angiotensin receptor antagonist are consistent with the proposal that sodium appetite of the sodium-deplete rat, adrenalectomized or intact, is mediated by circulating angiotensin II acting in the subfornical organ.     

Cloned human cytotoxic T lymphocytes develop anomalous killer cell function.

Mixed lymphocyte cultures were set up between blood mononuclear cells and irradiated autologous or allogeneic B lymphoblasts infected with Epstein-Barr virus. The resulting cytotoxic effector cells were cloned and tested for activity against the stimulating B lymphoblast, K562 and melanoma targets. Specific clones which killed only the stimulating B lymphoblasts (cytotoxic T lymphocytes; CTL) were re-cloned and the subclones tested for cytolysis of B lymphoblasts and melanoma cells. Of seven primary CTL clones generated in allogeneic culture, 308 subclones developed the ability to kill melanoma cells and none retained specific CTL function. In the autologous system, 180 subclones were derived from three specific primary clones: of these, 13 (7%) retained specific function, 29 (16%) were able to kill both B lymphoblasts and melanoma cells, and 93 (52%) killed only the melanoma target. Testing of random clones demonstrated that whereas both B lymphoblast killing (CTL function) and melanoma cell killing (anomalous killer; AK function) were blocked by a monoclonal antibody to LFA-1, only CTL function was blocked by anti-T3 or anti-T8 antibodies. The factor(s) causing the progression of CTL to AK cells are discussed. These data thus demonstrate that the majority of CTL are capable of mediating AK cell function and are thus potentially suitable for passive immunotherapy.     

Activated lymphocyte killer cells derived from melanoma tissue or peripheral blood

Lymphoid cells infiltrating metastatic melanomas were grown directly from cell suspensions of tumour tissue by the addition of T cell growth factor. Lymphoid cells grew out at the expense of tumour cells in six of seven freshly excised tumours, and cells from two cultures were expanded for in vitro testing of cytolytic function against different target cells. Early in culture the tumour derived lymphocytes killed fresh autologous melanoma cells and, particularly later in culture, were highly and non-specifically cytolytic for cultured melanoma and non-melanoma cells. Cultured peripheral blood lymphocytes from patients with melanoma, and from normal subjects, were cytolytic to the same degree as tumour derived lymphocytes, and also resembled cells grown from tumour tissue in possessing acid phosphatase activity which was resistant to tartrate. Cultured lymphoblasts from both tumour and peripheral blood had a T cell phenotype when analysed with monoclonal antibodies. An in vitro co-culture system was employed to study the kinetics and the precursors of these non-specific killer cells among blood mononuclear cells. Blood mononuclear cells cultured with irradiated B lymphoblasts led to the generation of non-specific cytolytic cells, referred to as activated lymphocyte killer (ALK) cells, after 7-10 days of culture and the progenitors of these ALK cells were demonstrated to be distinct from those of specific cytolytic T cells.     

Immune response to the B oligomer of pertussis toxin.

Immunization of mice with the B oligomer of pertussis toxin induced antibodies to the native toxin as measured by an enzyme-linked immunosorbent assay. These antibodies neutralized the ability of pertussis toxin to alter the morphology of Chinese hamster ovary cells. Furthermore, mice immunized with the B oligomer, when challenged with pertussis toxin, did not exhibit the leukocytosis normally associated with exposure to the toxin. These results demonstrate that the B oligomer, which does not contain the enzymatic activity of the holotoxin, can be used to induce a neutralizing antibody response and suggest that the B oligomer might be considered for use in acellular pertussis vaccines.