5 research outputs found
Interferon-Alpha Administration Enhances CD8+ T Cell Activation in HIV Infection
Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation.To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNΞ± for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNΞ± treatment.The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (pβ=β0.006). These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cellsβ=β2.62% at baseline and 2.17% after 12 weeks of interferon therapy). As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001).Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection
Patient Cohort from AIDS Clinical Trial Group Study 5192.
<p>Patient Cohort from AIDS Clinical Trial Group Study 5192.</p
Co-expression of CD38 and HLA-DR on CD4+ and CD8+ T cells.
<p>The percentage of CD4+ T cells (A) and CD8+ T cells (B) co-expressing CD38 and HLA-DR is shown over the course of interferon-alpha treatment during the ACTG 5192 Study. Week 0 corresponds to the patients' baseline cell counts before beginning Interferon-Alpha Therapy. Weeks 3 and 12 correspond to 3 weeks and 12 weeks of interferon-alpha Therapy. Interferon-Alpha therapy was stopped at Week 12, and therefore Week 18 corresponds to 6 weeks off therapy. The bar represents the median value.</p
CD4+ and CD8+ T cell counts.
<p>The CD4 Cell Count (A) and the CD8 Cell Count (B) are portrayed over the course of interferon-alpha treatment during the ACTG 5192 Study. Week 0 corresponds to the patients' baseline cell counts before beginning Interferon-Alpha Therapy. Weeks 3 and 12 correspond to 3 weeks and 12 weeks of interferon-alpha Therapy. Interferon-Alpha therapy was stopped at Week 12, and therefore Week 18 corresponds to 6 weeks off therapy.</p
Cell cycle status of CD4+ T cell maturation subsets.
<p>The cell cycle status of CD4+ T cell maturation subsets, Central Memory CD4 +T Cells (A), Naive CD4+ T cells (B), Transitional Memory CD4+ T cells (C), and Effector Memory CD4+ Tcells (D), is shown over the course of interferon-alpha treatment during the ACTG 5192 Study. Central memory cells were defined as CD 27+CD45RAβ and CCR7+, whereas naΓ―ve cells are CD27+, CD45RA+, and CCR7+, transitional memory cells are CD27+, CD45RAβ, and CCR7β, and effector memory cells are CD27β, CD45RAβ, and CCR7β. Week 0 corresponds to the patients' baseline cell counts before beginning Interferon-Alpha Therapy. Weeks 3 and 12 correspond to 3 weeks and 12 weeks of interferon-alpha therapy. Interferon-Alpha therapy was stopped at Week 12, and therefore Week 18 corresponds to 6 weeks off therapy. The bar represents the median value.</p