Association Between Innate Immunity and Memory in Immunization Against HIV or SIV Infection

HIV-1 is transmitted predominantly through mucosal tissues, and targets CD4+CCR5+ T cells, 50% of which are destroyed within 2 weeks. Conventional vaccination strategies have so far failed to prevent HIV-1 infection. Neither antibodies nor cytotoxic lymphocytes are capable of mounting a sufficiently rapid immune response to prevent early destruction of these cells. However, innate immunity is a rapid response system, largely independent of prior encounter with a pathogen. It can be divided into cellular, extracellular and intracellular innate immune components, exemplified by dendritic cells (DC), CC-chemokines and APOBEC3G, respectively. Stimulation with CD40L (CD154) or HSP70 induces maturation of human monocyte-derived DC, upregulates cell-bound IL-15, elicits cytokines, CC-chemokines, and APOBEC3G, which is an innate anti-HIV-1 immune factors. The major objective of this presentation is to demonstrate (a) that IL-15 expressed by DC may upregulate CD4+CD45RO+CD62- effector memory T cells. (b) CD8+ T cell derived CC-chemokines CCL-1, CCL-2 and CCL-3 can be upregulated by immunization of macaques with SIVgp120 and gag p27. (c) APOBEC3G can be generated and maintained following rectal mucosal immunization in rhesus macaques for over 21 weeks, and the innate anti-SIV factor is generated by CD4+CD95+CCR7- effector memory T cells. Thus, innate anti-HIV-1 or SIV immune functions are closely linked with immune memory mediated either by the CD8+ cells providing the extracellular CC-cytokines or by intracellular CD4+ T cells generating APOBEC3G, or DC expressing the IL-15 molecule, which can induce CD4+ effector memory T cells. The multiple innate functions may mount an early anti-HIV-1 response and either prevent viral transmission or contain the virus until an effective adaptive immune response develops.