Incorporation of innate immune effector mechanisms in the formulation of a vaccine against HIV-1.
ABSTRACT The realization of a major role for events that occur during acute viremia that dictate the course of disease both in HIV-1 infected humans and susceptible SIV infected non-human primates has prompted an intense interest in studies of the contribution of innate immune effector mechanisms. It is reasoned that findings from such studies may be important and need to be incorporated into the design and formulation of potential candidate vaccines against HIV-1. This review serves to outline the various non-human primate models that can best serve to address this issue, a summary of our knowledge on the various subsets of NK cells (one of the major innate immune cell lineage) that have an impact on the course of disease, the potential pathways that regulate their function and the potential role of the KIRs on SIV-induced disease course. Finally, the major points from this report and the data presented on similar subjects by other investigators is utilized to provide a summary of the potential future directions that we need to take in efforts to move this field forward.
- SourceAvailable from: ncbi.nlm.nih.gov[show abstract] [hide abstract]
ABSTRACT: NK cells are critical in the early containment of viral infections. Epidemiological and functional studies have shown an important role of NK cells expressing specific killer immunoglobulin-like receptors (KIRs) in the control of human immunodeficiency virus type 1 (HIV-1) infection, but little is known about the mechanisms that determine the expansion of these antiviral NK cell populations during acute HIV-1 infection. Here we demonstrate that NK cells expressing the activating receptor KIR3DS1(+) and, to a lesser extent, the inhibitory receptor KIR3DL1(+) specifically expand in acute HIV-1 infection in the presence of HLA-B Bw480I, the putative HLA class I ligand for KIR3DL1/3DS1. These data demonstrate for the first time the HLA class I subtype-dependent expansion of specific KIR(+) NK cells during an acute viral infection in humans.Journal of Virology 05/2009; 83(13):6798-805. · 5.08 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Since their discovery three decades ago, NK cells have been classified as cells of the innate immune system. NK cells were shown to respond rapidly and non-specifically to infection, and were thought to act as a functional "bridge" to sustain the early innate immune response until the later adaptive immune responses could be mounted. In light of new findings showing how NK cells possess nearly all of the features of adaptive immunity including memory, we propose the placement of NK cells as an "evolutionary bridge" between innate and adaptive immunity.European Journal of Immunology 08/2009; 39(8):2059-64. · 4.97 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIVDeltanef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4-10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5-10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIVDeltanef animals were predominantly CD27-CD28-CD45RAlowCCR7-CCR5-, consistent with an effector-memory subset, and included a fully differentiated CD45RA+CCR7- subpopulation. In contrast, SIV-specific CD4+ T cells from SIV-infected animals were mostly CD27+CD28+CD45RA-CCR7+CCR5+, consistent with an early central memory phenotype. The CD45RA+CCR7-CD4+ subset from SIVDeltanef animals was highly enriched for effector CD4+ T cells, as indicated by the perforin expression and up-regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4+ T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector-memory T cell population. The ability of SIVDeltanef to induce a high frequency virus-specific CD4+ T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.Journal of Experimental Medicine 12/2006; 203(12):2661-72. · 13.21 Impact Factor