Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we demonstrated that memory cell-mediated immune responses can be generated in Pichinde virus (PV)-primed mice after secondary challenge in vivo with homologous virus. Further, treatment of mice with cyclophosphamide (CY) before primary infection with PV abrogated the generation of H-2-restricted, virus-specific cytotoxic T lymphocytes (CTL), and rechallenge of these mice was followed by neither a primary nor a secondary CTL response. Here, we demonstrate that this CY-induced block in memory anti-PV CTL generation was not due to establishment of a persistent infection. Interestingly, this CY-induced block in memory anti-PV CTL generation was overcome by secondarily coinfecting mice with PV and lymphocytic choriomeningitis virus (LCMV) or PV and Tacaribe virus. Secondary infection with LCMV or Tacaribe virus alone did not elicit anti-PV CTL. Coinfection resulted in the generation of a PV-specific memory CTL response as judged by maximal activity on day 4 after rechallenge. Co-infection with PV and vesicular stomatitis virus, an unrelated rhabdovirus, did not efficiently restore memory anti-PV CTL responses. Memory anti-PV CTL responses were also restored when interleukin 2 (IL 2)-containing supernatants were injected i.p. after rechallenge of CY-treated mice with PV. To demonstrate that IL 2 was the responsible lymphokine in these preparations, highly purified IL 2 was added to in vitro cultures of spleen cells from CY-treated PV-primed mice. In the presence of PV-infected syngeneic macrophages, addition of purified IL 2 resulted in a dose-dependent restoration of H-2-restricted anti-PV CTL activity. The CTL precursor (CTLp) frequency of CY-treated PV-primed mice was markedly decreased from that of normal PV-primed mice. Thus, the long-lasting block in the ability to generate a PV-specific memory CTL response after CY treatment appears to be due to both a lack of helper T cell activity and a significant reduction of CTLp. However, this block may be overcome by coinfecting with viruses that cross-react at the helper T cell level or by exogenous treatment with highly purified IL 2.
 ...
PMID:Abrogation of anti-Pichinde virus cytotoxic T cell memory by cyclophosphamide and restoration by coinfection or interleukin 2. 298 65

The abilities of Escherichia coli-derived human interferon gamma (IFN-gamma) and E. coli-derived human interferon-alpha A (IFN-alpha A) or -alpha 2 (IFN-alpha 2) to augment natural killer (NK) cytotoxicity were compared. When low concentrations (less than 10 antiviral units/ml) of interferons were used, and equal numbers of antiviral units of E. coli-derived IFN-gamma and E. coli-derived IFN-alpha A or IFN-alpha 2 were compared for their ability to augment NK, E. coli-derived IFN-gamma was found to be more active in augmenting NK against the K562 targets, than E. coli-derived IFN-alpha A or IFN-alpha 2. Antiviral units in these experiments were determined by the standard cytopathic effect assay using vesicular stomatitis virus (VSV)-challenged human fibroblasts, trisomic for chromosome 21. However, when these interferons were compared on a weight basis (ng/ml) or on a molar basis, their ability to augment NK against the K562 targets was comparable. These differences in the relative abilities of these interferons (when their concentrations were expressed in antiviral units/ml) to augment NK, were due to an approximately 100-fold difference in their specific activities (antiviral units per mg of interferon). These were 1.8 X 10(6) units/mg for E. coli-derived IFN-gamma, 2.0 X 10(8) units/mg for E. coli-derived IFN-alpha A, and 1.8 X 10(8) units/mg for E. coli-derived IFN-alpha 2. At concentrations higher than 10 units/ml, all these interferons showed a similar ability to augment NK. Studies on the kinetics of the augmentation revealed that in vitro treatment with E. coli-derived IFN-gamma for several hours was necessary for augmentation of NK against targets from haemopoietic human tumour cell lines (K562, Daudi). In contrast, alpha interferons were able to augment NK after treatment in vitro for significantly shorter periods (30 min or less with certain donors). Augmentation of NK cytotoxicity of human peripheral blood mononuclear leucocytes by E. coli-derived IFN-gamma was not accompanied by the induction of interleukin 2 (IL-2) production, suggesting that IL-2 is not involved in the augmentation of NK by IFN-gamma. A monoclonal antibody specific for human IFN-gamma blocked augmentation of NK by E. coli-derived IFN-gamma and natural IFN-gamma, but not by E. coli-derived IFN-alpha A or staphylococcal enterotoxin A (SEA).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Regulation of natural killer cytotoxicity by Escherichia coli-derived human interferon gamma. 308 22

Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytotic cells of the myeloid lineage. Natural killer (NK) cells are spontaneously cytotoxic large granular lymphocytes that are involved in immunosurveillance against cancer and infections. Their activity is modulated by hormones of the hypothalamic-pituitary-adrenal axis. We wished to determine whether two human corticostatins/defensins, HP-1 and HP-4, are able to change in vitro the spontaneous NK activity of human peripheral blood mononuclear cells (PBMC) and the responses either to the stimulatory cytokines immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory hormone cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay with K562 cells as a target. HP-1 and HP-4 (10 (-8) -10 (-9) M) significantly inhibited the spontaneous and cytokine-inducible NK activity, and increased the cortisol-dependent inhibition. Radioimmunoassay of HPLC purified fractions obtained from sonicated NK cells showed HP-1 in the two cell preparations examined. We also evaluated the effects of HP-1 and HP-4 (10 (-8) M -10(-9) M) upo IFN-gamma and interleukin 6 (IL-6) production by PBMC stimulated with phytohemagglutinin (PHA) or concanavalin A (ConA). IFN-gamma was titrated with the biological assay using WISH cells as indicators and vescicular stomatitis virus (VSV) as the challenge virus. IL-6 was measured using an enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that corticostatins/defensins are novel modulators of lymphocyte functions in vitro. Their immunodepressing properties could add complexity and plasticity to hypothalamic-pituitary-adrenal-cytokine circuits in vivo.
 ...
PMID:Corticostatins/defensins inhibit in vitro NK activity and cytokine production by human peripheral blood mononuclear cells. 873 77