Contrasting Effects of Low-Dose IL-2 on Vaccine-Boosted Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cells in Macaques Chronically Infected with SIVmac251

Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892, USA.
The Journal of Immunology (Impact Factor: 5.36). 03/2005; 174(4):1913-21. DOI: 10.4049/jimmunol.174.4.1913
Source: PubMed

ABSTRACT IL-2, the first cytokine discovered with T cell growth factor activity, is now known to have pleiotropic effects on T cells. For example, it can promote growth, survival, and differentiation of Ag-selected cells, or facilitate Ag-induced cell death of T cells when Ag persists, and in vivo, it is thought to contribute to the regulation of the size of adaptive T cell response. IL-2 is deficient in HIV-1 infection and has been used in the management of HIV-1-infected individuals undergoing antiretroviral therapy. In this study, we investigated how continuous low-dose IL-2 affected the CD4+ and CD8+ T cell response induced by two inoculations of a canarypox recombinant SIV-based vaccine candidate in healthy macaques chronically infected with SIVmac251. These macaques had normal levels of CD4+ T cells at the beginning of antiretroviral therapy treatment. Vaccination in the presence of IL-2 significantly augmented Gag-specific CD8+ T cell responses, but actually reduced Gag-specific CD4+ T cell responses. Although IL-2 at low doses did not change the overall concentration of circulating CD4+ or CD8+ T cells, it expanded the frequency of CD4+CD25+ T cells. Depletion of the CD4+CD25+ T cells in vitro, however, did not result in a reconstitution of Gag-specific CD4+ responses or augmentation of SIV-specific CD8+ T cell responses. Thus, we conclude that the decrease in virus-specific CD4+ T cell response may be due to IL-2-promoted redistribution of cells from the circulation, or due to Ag-induced cell death, rather than suppression by a T regulatory population.

  • Source
    • "The importance of virus-neutralizing Ab, CTL and Th cells elicited by HIV or its simian equivalent (SIV) have been recognized in numerous studies [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The difficulty in developing an effective vaccine to contain the HIV/AIDS epidemic coupled with the fact that primary HIV-1 infection typically occurs via mucosal sites has increased emphasis on vaccine approaches that protect at mucosal surfaces. In this study we employed HIV and simian-HIV (SHIV)-derived T helper (Th) and cytotoxic T lymphocyte (CTL) single epitopes incorporated into immuno-stimulating complexes (ISCOM) as a candidate immunogens. Immunized rhesus macaques (Macaca mulatta) were challenged with CCR5-tropic SHIV(SF162p4). On the day of challenge, low levels of virus-neutralizing antibodies (Ab) and CTLs were detected in ISCOM-immunized macaques. Greater than 10(5) viral RNA copies per ml of plasma in 2/5 immunized and 3/4 control macaques were detected within 3 weeks post-challenge. Depletion of CD4+ T cells from gut-associated lymphoid tissues (GALT) was observed by post-challenge day (PCD) 14 in all macaques regardless immunization. Nonetheless, lower viral loads and relatively better preservation of peripheral CD4+ T cells following the SHIV infection was observed in ISCOM-immunized macaques. We predict that if coadministered with additional epitopes and/or more efficacious mucosal delivery system or route, HIV/SIV-derived peptide vaccines may have potential to elicit heterologous protection.
    Vaccine 12/2006; 24(47-48):6839-49. DOI:10.1016/j.vaccine.2006.06.050 · 3.49 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Agents that activate dendritic cells are essential components for vaccines and can be conceptualized as molecular adjuvants. Other molecular adjuvants affect downstream factors that shape the resulting immune response. This review provides a compendium of recently studied molecular adjuvants, focusing on CD8+ T cell responses, which have important roles in HIV vaccines. Reference is also made to CD8+ T cell antitumor responses, where parallel studies of molecular adjuvants are being pursued. Molecular adjuvants can be considered in the following groups: TNF superfamily molecules such as CD40 ligand; agonists for TLRs; agonists for NAIP, CIITA, HET-E, TP-1-leucine-rich repeat pathway receptors, such as nucleotide-binding and oligomerization domain (NOD)1, NOD2, and cryopyrin; chemokines; ILs; CSFs; IFNs; alarmins; and purinergic P2X7 receptor agonists. Complementing these positively acting agents are strategies to reduce the immunosuppressive effects of CD4+CD25+ regulatory T cells and negatively acting factors such as TGF-beta, IL-10, suppressor of cytokine signaling 1, and programmed cell death-1 using neutralizing antibodies, antisense, and small interfering RNA. Especially effective are combinations of molecular adjuvants, which can elicit a massive expansion of antigen-specific CD8+ T cells and show unprecedented efficacy in vaccine and tumor models. Taken together, these new approaches provide significant incremental progress in the development of vaccines to elicit cell-mediated immunity against HIV and other pathogens.
    Journal of Leukocyte Biology 12/2006; 80(5):1084-102. DOI:10.1189/jlb.0306147 · 4.30 Impact Factor
Show more


Available from