Distinctive in vitro effects of T-cell growth cytokines on cytomegalovirus-stimulated T-cell responses of HIV-infected HAART recipients.
Functional immune reconstitution is limited after HAART, maintaining the interest in adjunctive immune-modulators. We compared in vitro the effects of the gamma-chain T-cell growth cytokines IL-2, IL-4, IL-7 and IL-15 on cytomegalovirus-stimulated cell-mediated immunity. IL-2 and IL-15 increased cytomegalovirus-specific lymphocyte proliferation in HAART recipients, whereas IL-4 and IL-7 did not. The boosting effect of IL-2 and IL-15 on proliferation correlated with their ability to prevent late apoptosis. However, IL-2 increased the frequency of cells in early apoptosis, whereas IL-15 increased the frequency of fully viable cells. Both IL-2 and IL-15 increased cytomegalovirus-induced CD4+ and CD8+ T-cell proliferation and the synthesis of Th1 and pro-inflammatory cytokines and chemokines. However, only IL-2 increased the frequency of regulatory T cells and Th2 cytokine production, both of which have the potential to attenuate antiviral immune responses. Overall, compared to other gamma-chain cytokines, IL-15 had the most favorable profile for boosting antiviral cell-mediated immunity.
Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262, USA.
Julie
J
Patterson
Renee
R
Jesser
Adriana
A
Weinberg
D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D003587:Cytomegalovirus / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D019409:Interleukin-15 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D007378:Interleukins / Q000008:administration & dosage / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D019409:Interleukin-15; D007378:Interleukins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12