Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclear leukocytes.
(9/3155)
It has been recently shown that Fas ligand (FasL) expression on islet beta grafts results in neutrophilic infiltration and graft rejection. In this study, we show that human recombinant soluble FasL is endowed with potent chemotactic properties toward human neutrophilic polymorphonuclear leukocytes (neutrophils) at concentrations incapable of inducing cell apoptosis. Furthermore, neutrophils exposed to soluble FasL did not display detectable change of intracellular Ca2+ and did not undergo superoxide production or exocytosis of primary and secondary granules. Our results show that FasL is a potent chemoattractant for human neutrophils without evoking their secretory responses. This finding suggests a novel proinflammatory function for this ligand and may help to clarify the mechanism governing FasL-mediated graft rejection, thereby offering rational bases for controlling and modulating FasL-based immunotherapies. (+info)
Leucocyte aggregation in subjects with nickel dermatitis.
(10/3155)
The effect of nickel sulphate on leuco-aggragation in whole blood buffy coat layers was studied in nickel-sensitive and control subjects. At concentrations of 150 mug and 200 mug nickel sulphate per ml a significant increase in the numbers of leuco-aggregates was noted in the nickel sensitive as compared with the control subjects. (+info)
Immunity to Brucella in mice vaccinated with a fraction (F8) or a killed vaccine (H38) with or without adjuvant. Level and duration of immunity in relation to dose of vaccine, recall injection and age of mice.
(11/3155)
Immunity to Brucella in the mouse, assessed by bacterial spleen counts 15 days after intraperitoneal inoculation of a standard challenge of B. abortus 544, has been studied with two vaccines, one experimental, composed of a fraction of the bacterial cell-wall (F8) extracted from B. abortus 99, the other of killed whole bacteria, B. melitensis 53 H38, taken as reference (H38). The level of primary immunity depended on the dose of vaccine, the presence of oil adjuvant and the age of the mouse. The presence of adjuvant enabled the immunization to F8 to continue beyond the first month, to reach its maximum around the fourth month, and to remain stable for at least 7 months. A booster injection 3 or 6 months after the primary vaccination reinforced existing immunity but did not increase it beyond a certain level. The effect of the recall injection was clearly demonstrated with low doses which gave a lower level of primary immunity. (+info)
Factors associated with the development of neonatal tolerance after the administration of a plasmid DNA vaccine.
(12/3155)
A plasmid DNA vaccine encoding the circumsporozoite protein of malaria (pCSP) induces tolerance rather than immunity when administered to newborn mice. We find that this tolerance persists for >1 yr after neonatal pCSP administration and interferes with the induction of protective immunity in animals challenged with live sporozoites. Susceptibility to tolerance induction wanes rapidly with age, disappearing within 1 wk of birth. Higher doses of plasmid are more tolerogenic, and susceptibility to tolerance is not MHC-restricted. CD8+ T cells from tolerant mice suppress the in vitro Ag-specific immune response of cells from adult mice immunized with pCSP. Similarly, CD8+ T cells from tolerant mice transfer nonresponsiveness to naive syngeneic recipients. These findings clarify the cellular basis and factors contributing to the development of DNA vaccine-induced neonatal tolerance. (+info)
Adjuvant-guided type-1 and type-2 immunity: infectious/noninfectious dichotomy defines the class of response.
(13/3155)
Traditionally, protein Ags have been injected in CFA (oil with inactivated mycobacteria) to induce immunity and with IFA (oil alone) to induce tolerance. We report here that injection of hen eggwhite lysozyme, a prototypic Ag, in CFA-induced and IFA-induced pools of hen eggwhite lysozyme-specific memory T cells of comparable fine specificity, clonal size, and avidity spectrum, but with type-1 and type-2 cytokine signatures, respectively. This adjuvant-guided induction of virtually unipolar type-1 and type-2 immunity was observed with seven protein Ags and in a total of six mouse strains. Highly polarized type-1 and type-2 immunity are thus readily achievable through the choice of adjuvant, irrespective of the genetic bias of the host and of the nature of the protein Ag. This finding should have far-reaching implications for the development of vaccines against infectious and autoimmune diseases. Furthermore, our demonstration that Ag injected with IFA is as strongly immunogenic for T cells as it is with CFA shows that the presence of the mycobacteria determines not the priming of naive T cells through the second-signal link but the path of downstream differentiation toward CD4 memory cells that express either type-1 or type-2 cytokines. (+info)
In vitro analysis of complement-dependent HIV-1 cell infection using a model system.
(14/3155)
Previous studies based on the use of human serum as a source of C have provided evidence for the C-dependent enhancement of cell infection by HIV-1. The present study was undertaken to distinguish C from other serum factors and to identify the proteins and the mechanisms involved in C-dependent cell infection by HIV-1. The classical C activation pathway was reconstituted from the proteins C1q, C1r, C1s, C4, C2, C3, factor H, and factor I; each were purified to homogeneity. A mixture of these proteins at physiological concentrations was shown to reproduce the ability of normal human serum to enhance the infection of MT2 cells by HIV-1 at low doses of virus. This enhancing effect was abolished when heat-inactivated serum and C2- or C3-depleted serum were used, and was restored upon addition of the corresponding purified proteins. A mixture of two synthetic peptides corresponding to positions 10-15 and 90-97 of human C receptor type 2 (CD21) as well as soluble CD4 both inhibited the C-dependent infection process. These data provide unambiguous evidence that HIV-1 triggers a direct activation of the classical C pathway in vitro and thereby facilitates the infection of MT2 cells at low doses of virus. These findings are consistent with a mechanism involving increased interaction between the virus opsonized by C3b-derived fragment(s) and the CD21 cell receptors and subsequent virus entry through CD4 receptors. (+info)
Dose dependence of CTL precursor frequency induced by a DNA vaccine and correlation with protective immunity against influenza virus challenge.
(15/3155)
Intramuscular injection of BALB/c mice with a DNA plasmid encoding nucleoprotein (NP) from influenza virus A/PR/8/34 (H1N1) provides cross-strain protection against lethal challenge with influenza virus A/HK/68 (H3N2). CTL specific for the H-2Kd-restricted epitope NP147-155 are present in these mice and are thought to play a role in the protection. To assess the effectiveness of NP DNA immunization in comparison with influenza virus infection in the induction of CTL responses, we monitored the frequency of CTL precursors (CTLp) in mice following i.m. injection with NP DNA or intranasal infection with influenza virus and showed that the CTLp frequency in NP DNA-immunized mice can reach levels found in mice that had been infected with influenza virus. We also measured the CTLp frequency, anti-NP Ab titers, and T cell proliferative responses in mice that were injected with titrated dosages of NP DNA and documented a correlation of the CTLp frequency and the Ab titers, but not proliferative responses, with the injection dose. Furthermore, we observed a positive correlation between the frequency of NP147-155 epitope-specific CTLp and the extent of protective immunity against cross-strain influenza challenge induced by NP DNA injection. Collectively, these results and our early observations from adoptive transfer experiments of in vitro activated lymphocytes from NP DNA-immunized mice suggest a protective function of NP-specific CTLp in mice against cross-strain influenza virus challenge. (+info)
Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages.
(16/3155)
Although the metalloproteinase murine metalloelastase (MME) has been implicated in lung disorders such as emphysema and pulmonary fibrosis, the mechanisms regulating MME expression are unclear. Low m.w. fragments of the extracellular matrix component hyaluronan (HA) that accumulate at sites of lung inflammation are capable of inducing inflammatory gene expression in macrophages (Mphi). The purpose of this study was to examine the effect of HA fragments on the expression of MME in alveolar Mphi. The mouse alveolar Mphi cell line MH-S was stimulated with HA fragments over time, total RNA was isolated, and Northern blot analysis was performed. HA fragments induced MME mRNA in a time-dependent fashion, with maximal levels at 6 h. HA fragments also induced MME protein expression as well as enzyme activity. The induction of MME gene expression was specific for low m.w. HA fragments and dependent upon new protein synthesis; it occurred at the level of gene transcription. We also examined the effect of HA fragments on MME expression in inflammatory alveolar Mphi from bleomycin-injured rat lungs. Although normal rat alveolar Mphi did not express MME mRNA in response to HA fragments, alveolar Mphi from the bleomycin-treated rats responded to HA fragment stimulation by increasing MME mRNA levels. Furthermore, baseline and HA fragment-induced MME gene expression in alveolar Mphi from bleomycin-treated rats was inhibited by IFN-gamma. These data suggest that HA fragments may be an important mechanism for the expression of MME by Mphi in inflammatory lung disorders. (+info)