ADVANCE AUSTRALIA FAIR? (IN)EQUALITY, PROSPERITY AND SUSTAINABILITY IN SHAPING AUSTRALIA’S FUTURE

Scholarships & Prizes Office. University of Sydne

Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication among HCV seroconverters

AbstractThe objective of this retrospective cohort study is to assess the mechanism by which human immunodeficiency virus type 1 (HIV) influences hepatitis C virus (HCV) replication in injecting drug users. Virological (HCV and HIV RNA levels) and immunological (CD4+, CD8+cell counts, and anti-CD3 reactivity) parameters were determined in 19 HCV seroconverters in sequential samples over a period of 1 to 9 years. Among these subjects, 10 were HIV-seronegative (HIVneg), 4 were HIV-seropositive (HIVpos), and 5 seroconverted for HIV (HIVsc) during the observation period. HCV RNA levels were higher in HIVpos subjects than in HIVneg subjects. In subjects seroconverting for HIV, HCV RNA levels increased significantly immediately after HIV seroconversion (P< 0.0001), while they remained stable over time in HIVpos and HIVneg subjects. HCV RNA correlated inversely with CD4+cell counts in both the HIVpos population (R= −0.22,P< 0.05) and the HIVneg population (R= −0.45,P< 0.0001). In addition, when subjects were stratified according to CD4+cell counts a significant difference was found in HCV RNA levels between HIVpos and HIVneg subjects with CD4+cell counts >500 cells/μl (P= 0.001), but not in the population with CD4+cell counts <500 cells/μl. In no population was a correlation found between HCV RNA levels and CD8+cell counts or anti-CD3 reactivity. Both HIV infection and CD4+cell counts are apparently associated with HCV RNA levels. The direct association, independent of CD4+cell counts, between HIV infection and HCV replication appears to be stronger than the association between HIV-induced CD4+cell decline and HCV replication. We conclude that (i) HCV replication is in some way directly influenced by the presence of HIV; (ii) HCV-specific host immunity controls, in part, HCV replication; and (iii) HCV replication increases when the immune system is impaired by HIV

Changes in the composition of circulating CD8+ T cell subsets during acute Epstein-Barr and human immunodeficiency virus infections in humans

In response to viral infection, unprimed naive CD8(+), major histocompatibility complex class I-restricted, virus-specific T cells clonally expand and differentiate into memory- and effector-type cells. Changes in CD8(+) subset distribution were studied in 17 subjects with acute human immunodeficiency virus type 1 infection and in 14 subjects with acute Epstein-Barr virus (EBV) infection, with combined CD45RO, CD27, and CD28 monoclonal antibodies. A vast expansion of memory-type CD45RO(+)CD27(+)CD8(+) T cells, with high expression of the cell-cycle marker Ki-67, was observed in both infections. Strikingly, CD45RO(+)CD27(+)CD28(-) cells increased >10-fold in acute viral infection and had high Ki-67 expression. In acute EBV infection, a substantial portion of the expanded T cells were EBV-peptide specific. These cells resided mainly in the CD45RO(+)CD27(+) subpopulation, with most in the CD27(+)CD28(-) subpopulation. Content of perforin expression, as a measure of cytotoxic capacity, was relatively low in the CD27(+)CD28(+) T cells and highest in the CD27(-)CD28(-) subpopulatio

Kawasaki disease: a maturational defect in immune responsiveness

Kawasaki disease (KD), an acute febrile disease in children of unknown etiology, is characterized by a vasculitis that may result in coronary artery aneurysms (CAAs). In new patients with KD, a selective and prolonged T cell unresponsiveness to activation via the T cell antigen receptor CD3 was observed, whereas proliferation to other stimuli was intact. This "split T cell anergy" delineated KD from other pediatric infections and autoimmune diseases and correlated with CAA formation (P <.001). A transient immune dysfunction was also suggested by an incomplete responsiveness to measles-mumps-rubella (MMR) vaccination in patients with KD versus controls (P <.0001; odds ratio, 15.6; 95% confidence interval, 4.8-51.1), which was overcome by revaccination(s). The reduced responsiveness to MMR in patients with KD suggests a subtle and predetermining immune dysfunction. An inherent immaturity to clear certain antigens may be an important cause that precipitates KD and the immune dysregulation during acute diseas

In vivo delayed-type hypersensitivity skin test anergy in human immunodeficiency virus type 1 infection is associated with T cell nonresponsiveness in vitro

In a cross-sectional study, the prevalence of delayed-type hypersensitivity skin test anergy (DTHA) was examined in 136 asymptomatic human immunodeficiency virus-infected participants in relation to immunologic and virologic parameters. DTHA was assessed with a multitest cell-mediated immunity skin test. Of the 136 participants, with a mean CD4 T cell count of 335 x 10(6)/L, 25 were anergic (18.4%). In the stepwise forward multivariate logistic regression models, after adjustment for CD4 T cell counts, depending on whether it was analyzed continuously or after dichotomization (20th percentile), both T cell reactivity to CD2 plus CD28 antibodies or to CD3 antibodies were the most predictive markers of DTHA (odds ratio, 0.80; 95% confidence interval, 0.67-0.94; and odds ratio, 2.97; 95% confidence interval, 1.1-8.3, respectively). This study shows a strong correlation between the decreased T cell responses in vitro and DTHA. Therefore, next to DTHA testing, T cell function assays may be useful to test immune reconstitution observed during antiretroviral treatmen