ABSTRACT
Interleukin-2 has been widely used in HIV-1+ subjects as an immunoactivating agent. In this study, we investigated cytokine production, Ki67 antigen expression and the modulation of the surface phenotype of the CD4/CD25+ subset as compared to the reciprocal CD4/CD25- subset in IL-2-treated HIV+ patients. Our findings suggest that CD4 T cells are heterogeneous in responding to IL-2, because CD4/CD25+ cells sharply increased their "memory" phenotype, their Ki67 antigen expression and were the main in vivo targets for IL-2-dependent proliferation during therapy, while the percentages of IFN-gamma+ (terminally differentiated) cells remained unchanged at the end of therapy. Conversely, the CD4+/CD25- subpopulation showed an expansion of differentiated cells and a slight increase in the proliferation rate. The use of anti-retroviral therapy alone (HAART) reduced the proliferation and increased the differentiation of both CD4 subsets. Our data suggest that IL-2 has a moderate capacity to activate resting T cells in vivo and is probably unable to boost HIV-1 from latency to the replicative state.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , Cytokines/drug effects , HIV Infections/drug therapy , Interleukin-2/pharmacology , Adult , Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/metabolism , Cell Differentiation/drug effects , Cell Division/drug effects , Cell Division/physiology , Cytokines/biosynthesis , HIV Infections/immunology , Humans , Indinavir/administration & dosage , Interferon-gamma/biosynthesis , Interferon-gamma/drug effects , Interleukin-2/administration & dosage , Interleukin-2/analogs & derivatives , Interleukin-2/therapeutic use , Receptors, Interleukin-2/metabolism , Recombinant Proteins/administration & dosageABSTRACT
Presence of the Human Herpesvirus 8 (HHV8) genome has been reported in the bone marrow of multiple myeloma (MM) patients. So far, serological studies of HHV8 and MM have been inconsistent but have not included prospective epidemiological studies. We evaluated whether HHV8 infection is associated with increased risk for MM in a prospective population-based study of 39 000 Finnish subjects who donated serum samples in the period 1968-72. Serum samples from 47 subjects who developed MM during a 23-year follow-up and 224 age, area of residence and sex-matched subjects who remained healthy over a similar follow-up period were evaluated for HHV8 antibodies at enrollment, as assayed both with an immunofluorescence assay (IFA) for lytic and latent HHV8 antigens and by Western blot (WB) with three recombinant HHV8 proteins (ORFs 65, 73 and K8.1A). HHV8 seropositivity for at least one HHV8 protein on WB was found in 7% of the Finnish population and was not associated with the risk of developing MM (Relative Risk (RR) = 0.89, Confidence Interval (CI): 0.25-3.25). HHV8 seropositivity for lytic and latent antigens in the IFA was found in 16% and 0.4% of the Finnish population and tended to associate with risk of MM (RR = 2.02, CI: 0.94-4.33 and RR = 10.00, CI: 0.91-110.29, respectively). In conclusion, no statistically significant evidence for an association between HHV8 infection and the risk of future MM was found.