作者：
Bertoletti, AMaini, MKUCL
Sch Med Inst Hepatol London WC1E 6HX England UCL
Sch Med Dept Sexually Transmitted Dis Mortimer Market Ctr London WC1E 6AU England
During infection with hepatitis B or C viruses, cytotoxic T lymphocytes (CTLs) have been implicated as both the mediators of protection and the principal effecters of liver pathology. Recent studies have allowed an in...
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During infection with hepatitis B or C viruses, cytotoxic T lymphocytes (CTLs) have been implicated as both the mediators of protection and the principal effecters of liver pathology. Recent studies have allowed an investigation of the relationship between virus-specific CTL responses, liver damage and viral replication. In the presence of an efficient virus-specific CTL response, a scenario is emerging where inhibition of viral replication can be independent of liver pathology. We discuss the possibility that an inadequate CTL response - unable to control viral replication - may contribute to liver pathology not only directly but also via the recruitment of non-virus-specific T cells.
Despite initial virus control by CD8(+) cytotoxic T lymphocytes (CTLs), noncytopathic or variably cytopathic viruses (e.g., hepatitis B and C viruses, HIV) are able to establish persistent infections. The role of neut...
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Despite initial virus control by CD8(+) cytotoxic T lymphocytes (CTLs), noncytopathic or variably cytopathic viruses (e.g., hepatitis B and C viruses, HIV) are able to establish persistent infections. The role of neutralizing antibodies (nAbs) in controlling disease progression is unclear. Therefore, the phenomenon of viral evasion from the nAb response and its implications for virus persistence remain controversial. Here we demonstrate nab-mediated viral clearance in CTL-deficient mice infected with the prototypic noncytopathic lymphocytic choriomeningitis virus (strain WE). During prolonged CTL absence, neutralization-resistant virus mutants were selected in individual mice within 70-90 days. In naive animals infected with these virus variants only low nAb responses were induced, resulting in an increased tendency of virus to persist.
Human T helper (ih) cells (Th1- or Th2-oriented memory T cells as well as Th1- or Th2-polarized naive T cells) were infected in vitro with an RS-tropic HIV-1 strain (BaL) and assessed for their profile of cytokine pro...
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Human T helper (ih) cells (Th1- or Th2-oriented memory T cells as well as Th1- or Th2-polarized naive T cells) were infected in vitro with an RS-tropic HIV-1 strain (BaL) and assessed for their profile of cytokine production, CCR5 receptor expression, and HIV-1 p24 antigen (p24 Ag) production. Higher p24 Ag production was found in CCR5-negative Th2-like memory T cells than in CCR5-positive Th1-like memory T cells. By contrast, p24 Ag production was higher in Th1-polarized activated naive T cells in the first 4 days after infection. However, p24 Ag production in Th1-polarized T cells became comparable or even lower than the production in Th2-polarized populations later in infection or when the cells were infected with HIV-1BaL after secondary stimulation. The higher levels of p24 Ag production by Th1-polarized naive T cells soon after infection reflected a higher virus entry, as assessed by the single round infection assay using the HIV-chloramphenicol acetyl transferase (HIV-CAT) RS-tropic virus that contains the envelope protein of HIV-I YU2 strain. The limitation of viral spread in the Th1-polarized populations, despite the initial higher level of T-cell entry of RS-tropic strains, was due to the ability of Th1 cells to produce greater amounts of beta-chemokines than Th2 cells. In fact, an inverse correlation was observed between Th1-polarized naive T cells and Th1-like memory-activated T cells in regards to p24 Ag production and the release of the following CCR5-binding chemokines: regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta, Moreover, infection with the HIV-1 Bat strain of Th1-polarized T cells in the presence of a mixture of anti-RANTES, anti-MIP-1 alpha, and anti-MIP-1 beta neutralizing antibodies resulted in a significant increase of HIV-1 expression. These findings suggest that Th1-type responses may favor CD4(+) T-cell infection by RS-tropic HIV-1 strains, but HIV-1
This study uses recombinant vaccinia viruses expressing truncated or entire bluetongue virus (BTV) proteins to map the location of epitopes recognized by cytotoxic T lymphocytes (CTL) from Australian merino sheep. The...
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This study uses recombinant vaccinia viruses expressing truncated or entire bluetongue virus (BTV) proteins to map the location of epitopes recognized by cytotoxic T lymphocytes (CTL) from Australian merino sheep. The non-structural protein, NS1, was recognised by CTL from all sheep, while VP2, VP3, VP5 and VP7 were recognised by CTL from only some sheep. The remaining proteins (except for VP1, which was not tested) did not contain CTL. epitopes. When truncated genes were used to map the location of CTL epitopes, it was found that sheep often have CTL that recognise more than one epitope in NS1 or VP2. Overall there was considerable diversity in the CTL recognition patterns in the sheep tested. (C) 1999 Harcourt Publishers Limited.
The treatment of Epstein-Barr virus (EBV)associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable chall...
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The treatment of Epstein-Barr virus (EBV)associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD, These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD.
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