Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphotoxin alpha-deficient (LTalpha-/-) mice, which lack lymph nodes and possess a disorganized spleen, develop dysfunctional CD8+ T cells upon HSV infection and readily succumb to herpes encephalitis. Such mice do develop apparently normal peptide-specific CD8+ T cell responses, as measured by MHC class I tetramer staining, but the majority of cells fail to become cytotoxic or express peptide-induced IFN-gamma production. In the present study, we demonstrate that functional defects of CD8+ T cells in LTalpha-/- mice can be largely rectified by the administration of plasmid DNA encoding CCR7 ligands before HSV infection. Treated mutant mice developed increased peptide-specific cytotoxic responses, enhanced numbers of CD8+ T cells capable of producing IFN-gamma, as well as improved resistance to HSV challenge. The corrective effect of chemokine treatment appeared to result from improved dendritic cell-mediated Ag presentation. Thus, a major consequence of the treatment was an increase in splenic dendritic cell number in CCR7 ligand-treated LTalpha-/- mice with such splenocyte populations showing improved APC activity in vitro. Our results document that functional defects of CD8+ T cells can be corrected, and indicate the value of plasmid vector encoding appropriate chemokines to achieve such immunotherapy.
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PMID:Plasmid DNA encoding CCR7 ligands compensate for dysfunctional CD8+ T cell responses by effects on dendritic cells. 1156 71

Professional APC play a central role in generating antiviral CD8(+) CTL immunity. However, the fate of such APC following interaction with these same CTL remains poorly understood. We have shown previously that prolonged Ag presentation persists in the presence of a strong CTL response following HSV infection. In this study, we examined the mechanism of survival of APC in vivo when presenting an immunodominant determinant from HSV. We show that transferred peptide-labeled dendritic cells were eliminated from draining lymph nodes in the presence of HSV-specific CTL. Maturation of dendritic cells with LPS or anti-CD40 before injection protected against CTL lysis in vivo. Furthermore, endogenous APC could be eliminated from draining lymph nodes early after HSV infection by adoptive transfer of HSV-specific CTL, yet the cotransfer of significant virus-specific CD4(+) T cell help promoted prolonged Ag presentation. This suggests that Th cells may assist in prolonging class I-restricted Ag presentation, potentially enhancing CTL recruitment and allowing more efficient T cell priming.
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PMID:CD4+ T cells can protect APC from CTL-mediated elimination. 1675 82

Ag presentation within the regional lymph node is crucial for the initiation of CD8+ T cell responses following viral infection. The magnitude and quality of the CD8+ T cell response are regulated by the interplay between the size of the APC population and duration of Ag presentation. To understand how these parameters are finely regulated during an immune response, we have investigated the dynamics of Ag presentation in influenza A virus and HSV-1 infection. In both infections, APC production was calculated to occur over the first few days of infection, after which there was slow exponential decay over a period of up to 2 wk. This production rate is most likely determined by the Ag availability and recruitment and/or maturation rate of dendritic cells. APC production was found to closely parallel lymph node cell recruitment in both infections. This was greatest in the first 6 h of infection for HSV and over the second and third day for influenza. In HSV infection, the peak production also coincides with peak viral levels. By contrast, in influenza infection, APC production ceased between the third and fourth day despite the presence of high levels of virus until 5 days after infection. These analyses demonstrate that two quite different self-limiting infections generate the APC necessary to drive T cell responses early in infection at different rates. Understanding how such contrasting kinetics of Ag presentation impacts on the growth and size of developing protective T cell populations has important implications for the design of vaccines and immunotherapies.
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PMID:Kinetics of major histocompatibility class I antigen presentation in acute infection. 1912 33