ISSN:0882-8245    

DOI:10.1089/vim.2000.13.1

年代:2000

数据来源: MAL

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.2

年代:2000

数据来源: MAL

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.3

年代:2000

数据来源: MAL

摘要:

ABSTRACTHIV induces disease only following chronic activation of the immune system. Other retroviruses such as the mouse mammary tumour virus (MMTV) activate a large percentage of T cells by encoding a superantigen (SAg). To date there is no evidence that HIV encodes a SAg. An alternative way to induce pan-activation of the immune system is by allogeneic stimulation, which occurs following transplantation. Here we extend previous work which demonstrated that HIVpgl20 could bind peptides in a similar manner to HLA, by demonstrating that human antigen presenting cells (APCs) expressing gp120 (but not DR1) can present a DRl-restricted peptide to induce proliferation of a DR1-restricted peptide-specific T-cell line in a similar manner to the same peptide presented by a DR1 expressing APC. Our data provide strong support for the hypothesis that the HLA-like regions of gp120 encode functional properties shared with HLA, and could explain the extraordinary clinical and immunological similarities between AIDS and chronic graft versus host disease.

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.9

年代:2000

数据来源: MAL

摘要:

ABSTRACTMonocytes represent a leukocyte subset that express high levels of CD14 on their surface (CD14-high). These cells play a critical role in the pathogenesis of HIV-1 infection. In the present study, we have identified a monocyte subset expressing an extremely low level of CD14 (CD14-low), and examined their susceptibility to HIV-1 infection. Phenotypic analysis by flow cytometry of these cells revealed a low level of CD4, but the absence of CD3, CD14, CD19, and CD83 surface markers. Both CD14-low and CD14-high cell populations expressed CD13 and CD33 markers on their surface, suggesting these cells to be of myeloid origin. Morphologically, CD14-low cells were indistinguishable from CD14-high cells. CD14-low cells were susceptible to infection with a monocytotropic strain of HIV-1 (HIVADA)- However, like CD14-high monocytes, CD14-low cells could not be productively infected with a T cell tropic strain of HIV-1 (H9/HTLVIIIB). Similar to CD14-high monocytes, CD14-low cells were capable of inducing antigen-stimulated CD4+T-cell proliferation. HIV-1 infection substantially reduced their ability to induce antigen-stimulated T-cell proliferation. These data indicate that CD14-low cells belong to the monocyte lineage and may play an important role in the immunopathogenesis of HIV-1 infection.

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.19

年代:2000

数据来源: MAL

摘要:

We have shown that genetically engineered mengoviruses containing artificially shortened 5′ noncoding poly(C) tracts (e.g., C0or C13UC10) are dramatically attenuated in adult Swiss/ICR mice when compared to wild-type virus or to a genetically engineered virus containing a wild-type length poly(C) tract (C44UC10). To explore further the relationship between poly(C) tracts and virulence, we have conducted more extensive characterizations of several engineered viruses in the murine model. Both short and long poly(C) tract viruses were highly virulent in newborn mice, underscoring the importance of age in poly(C)-mediated attenuation. Virus vMC24, with a tract sequence of C13UC10, was as attenuated in 4-week-old BALB/c, C.C3-H2k/LiMcdJ, and DBA/2 mice as in Swiss/ICR mice. But it was more pathogenic for C57BL/6 mice, and highly virulent for C3H/Hej and C3H/Hen mice, demonstrating the importance of murine genotype. As expected from its virulence in all mouse strains, vMwt, with a poly(C) of C44UC10, induced higher levels of viremia than vMC24. The vMwt also induced higher levels of circulating interferon and had reduced pathogenicity in chemically immunosuppressed Swiss/ICR mice. Similar immunosuppression did not increase the virulence of vMC24. Collectively, the data suggest that endogenous immune components and the immune competence of the host play significant roles in determining the susceptibility of mice to mengovirus infectio

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.27

年代:2000

数据来源: MAL

摘要:

ABSTRACTCytomegalovirus (CMV) has been associated with chronic graft rejection in solid organ transplant patients. To elucidate the mechanism by which CMV leads to graft rejection, we hypothesized that CMV infection of endothelial cells could stimulate alloreactive cytotoxic T lymphocytes (CTL). This hypothesis was explored using the following experimental model: peripheral blood mononuclear cells (MNC) obtained from normal hosts were grown on monolayers of umbilical vein endothelial cells (UVEC) infected with CMV (CMV-UVEC) or not (control) and tested for CTL activity against uninfected UVEC. We showed that CMV-UVEC-stimulated MNC have significant CTL activity against uninfected UVEC. The CTL activity elicited by CMV-UVEC stimulation was significantly higher compared with that stimulated by uninfected UVEC or by ganciclovir-treated CMV-UVEC, indicating the critical role of productive CMV infection. The CTL activity was specific for the UVEC used as stimulators and did not affect MHC-unrelated UVEC. However, lymphoblastoid lines (LBL) major histocompatibility complex (MHC)-identical with the stimulator UVEC were also killed by the CMV-UVEC-stimulated MNC. CTL killed identical UVEC and LBL in a competitive fashion. Blocking experiments with monoclonal antibodies (mAbs) identified CD4 cells as the main effector of CTL activity and MHC class I as the antigenic target of CTL. Although natural killer (NK) cells did not significantly contribute to the CTL activity of CMV-UVEC-stimulated MNC, their presence in the MNC cultures during the stimulation process was critical for the development of CTL. This model offers a framework for understanding the role of CMV infection in graft rejection and for devising preventative strategies.

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.37

年代:2000

数据来源: MAL

摘要:

AbstractThe safety and immunogenicity of four different regimens of CHIRON cytomegalovirus (CMV) gB subunit vaccine combined with MF59 adjuvant and administered to seropositive plasma donors were evaluated to ascertain whether vaccination of seropositive subjects would significantly increase antibody titer to gB glycoprotein. This was done to select the best vaccination regimen for generating high-titered plasma for manufacture of CMV immune globulin. No serious adverse events were attributed to this vaccine, and the vaccine was well tolerated. Only the first dose of vaccine in each regimen stimulated a four-fold or greater antibody response to gB glycoprotein and each regimen induced similar antibody titers. However, initial vaccination followed by a 1 week rest from plasmapheresis and two booster vaccinations at 8 and 24 weeks, each followed with another 1 week rest from plasmapheresis, maintained the highest geometric mean gB ELISA titer of the four regimens over the 34-week post-vaccination period. CMVIG manufactured from a pool of high titered plasma units from two of four subject groups had gB ELISA and neutralizing antibody titers nine and six times higher, respectively, compared to Cytogam, indicating that vaccination of seropositive subjects with CHIRON gB vaccine combined with MF59 adjuvant prior to harvesting plasma can enhance functional antibody in a CMVIG product.

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.49

年代:2000

数据来源: MAL

摘要:

ABSTRACTThe effects of recombinant interleukin-12 (rIL-12) on immune responses generated by subunit vaccines for respiratory syncytial virus (RSV) were evaluated in BALB/c mice. Parenteral co-administration of rIL-12 with F/AIOH or F/PBS resulted in accelerated clearance of infectious virus from the lungs 4 days after challenge. The immune responses elicited by 0.03 μg of F protein plus 10 ng of rIL-12 adsorbed to AIOH were more efficacious than those induced by 3 μg of F protein co-formulated with 1,000 ng of rIL-12 in PBS alone. Adsorption to AlOH prolonged the presence of rIL-12 in the sera. The resultant systemic humoral immune responses after vaccination with F/AIOH or G/AIOH were dependent on the dose of rIL-12 and characterized by heightened serum immunoglobulin G2a(IgG2a) antibody titers. Co-administration of rIL-12 with F/AIOH was also associated with diminished protein-specific IgE titers, elevated neutralizing antibody titers, and interferon-γ and (IFN-γ) in the sera, and enhanced antigen-dependent killer cell activity in the lungs after challenge. For maximum benefit, the data suggested that rIL-12 must be co-administered with F/AIOH. Collectively, the results indicated that rIL-12 directed immune responses toward a type 1 phenotype. However, examination of pulmonary inflammatory cells after challenge suggested that the type 1 phenotype was not absolute. Co-formulation with rIL-12 did not diminish pulmonary eosinophilia upon challenge of naive mice primed with F/AIOH, G/AIOH, or FI-RSV, and CD4+T cells were expanded relative to the CD8+T-cell compartment. These results are important for the future design of subunit vaccines against

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.57

年代:2000

数据来源: MAL

摘要:

ABSTRACTWe examined whether immunization with a single peptide induces cytotoxic T lymphocytes (CTLs) of heterogeneous specificities in vivo. Immunization of BALB/c mice with the peptide H2:529–537, which corresponded to amino acid residues 529–537 on the HA2 subunit transmembrane region of influenza A/Jap virus (H2N2) and possessed an H-2Kd-binding motif, induced CD8+CD4−CTLs. These CTLs lysed influenza A/Jap virus-infected target cells as well as those pulsed with the H2:529–537 peptide. H2:529–537 peptide-induced CTLs also lysed to lower but significant levels the target cells pulsed with the Hl:533–541 peptide, which corresponded to amino acid residues 533–541 on the HA2 subunit transmembrane region of influenza A/PR/8 virus (H1N1) and were compatible to H2:529–537.Immunization with the Hl:533–541 peptide, which also possessed an H-2Kd-binding motif, induced CTLsin vivo. Hl:533–541-induced CTLs lysed influenza A/PR/8 virus-infected target cells and those pulsed with the peptide Hl:533–541. Subtype cross-reactive CTLs to the H2:529–537 peptide were not induced by immunization with the Hl:533–541 peptide. Two peptides, H2:3S and H2:7S, which had one amino acid substitution, serine at the third and seventh positions, respectively, induced CTLs that lysed target cells pulsed with the respective peptides to the highest levels. These results indicate that immunization with a single peptide induces CTLs of heterogen

ISSN:0882-8245    

DOI:10.1089/vim.2000.13.73

年代:2000

数据来源: MAL