PubMed · 4594753
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Q N Myrvik. 1974. Adjuvants.. https://doi.org/10.1111/j.1749-6632.1974.tb28233.x
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Single-stranded RNA oligonucleotides containing an immunostimulatory motif (immunostimulatory RNA [isRNA]) are potent inducers of interferon-alpha via the Toll-like receptor 7. We investigated the effect of isRNA on the development of an immune response. We show that isRNA activates dendritic cells and induces production of Th1-type cytokines both in vitro and in vivo. Cytokine production led to bystander activation of T and B cells. We further demonstrate that isRNA triggers the generation of antigen-specific cytotoxic T cells and of an IgG2a-biased antibody response to antigen in a sequence-dependent manner. In summary, we provide evidence for the first time that isRNA oligonucleotides can simultaneously activate the innate and adaptive arms of the immune system.
We evaluated the ability of Lactobacillus delbrueckii UFV H2b20, a probiotic candidate, to stimulate the production of inflammatory cytokines and to induce macrophage activation and Th1 differentiation in peripheral blood mononuclear cells (PBMC) from healthy volunteers. Our results show that PBMC stimulated with heat-killed Lact. delbrueckii produced elevated levels of IL-12, IFN-gamma and TNF-alpha but no IL-10. IFN-gamma production was IL-12 dependent with NK cells as the main source. Furthermore, PBMC infected with Leishmania amazonensis presented elevated microbicidal activity when co-incubated with Lact. delbrueckii. Finally, Lact. delbrueckii was capable of inducing in vitro differentiation of L. amazonensis-specific Th1 cells. These findings suggest that this probiotic may be used as an adjuvant in vaccination protocols.
FTY720 is a novel immunosuppressant that improves the outcomes after solid organ and bone marrow transplantation (BMT) due to the sequestration of T cells into LN. We tested the hypothesis that the sequestration of donor T cells in LN by FTY720 would enhance their interaction with host APC, thus causing a greater degree of activation-induced apoptosis of alloreactive T cells, and thereby resulting in a reduction of graft-vs.-host disease (GVHD). The short-term administration of FTY720 improved the recipient survival after allogeneic BMT. FTY720 treatment facilitated a rapid contraction of the donor T cell pool in association with an increased degree of apoptosis of donor T cells. The donor T cell reactivity to host alloantigens was diminished in host's LN and adoptive transfer of donor T cells isolated from LN of FTY720-treated recipients of allogeneic BMT induced less severe GVHD in secondary recipients than the transfer from controls. Caspase-dependent apoptosis was involved in this mechanism because FTY720-induced protection was abrogated when a pan-caspase inhibitor was administered. These findings thus demonstrate the presence of a novel mechanism by which FTY720 modulates the allogeneic T cell responses: namely, by the induction of activation-induced apoptosis of alloreactive T cells in LN.