1 research outputs found
Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity
Background: T-cell tolerance of allergic cutaneous contact
sensitivity (CS) induced in mice by high doses of reactive hapten
is mediated by suppressor cells that release antigen-specific
suppressive nanovesicles.
Objective: We sought to determine the mechanism or
mechanisms of immune suppression mediated by the
nanovesicles.
Methods: T-cell tolerance was induced by means of intravenous
injection of hapten conjugated to self-antigens of syngeneic
erythrocytes and subsequent contact immunization with the same
hapten. Lymph node and spleen cells from tolerized or control
donors were harvested and cultured to produce a supernatant
containing suppressive nanovesicles that were isolated from the
tolerized mice for testing in active and adoptive cell-transfer
models of CS.
Results: Tolerance was shown due to exosome-like nanovesicles
in the supernatants of CD81 suppressor T cells that were not
regulatory T cells. Antigen specificity of the suppressive
nanovesicles was conferred by a surface coat of antibody light
chains or possibly whole antibody, allowing targeted delivery of
selected inhibitory microRNA (miRNA)–150 to CS effector T
cells. Nanovesicles also inhibited CS in actively sensitized mice
after systemic injection at the peak of the responses. The role of
antibody and miRNA-150 was established by tolerizing either
panimmunoglobulin-deficient JH2/2 or miRNA-1502/2 mice
that produced nonsuppressive nanovesicles. These nanovesicles
could be made suppressive by adding antigen-specific antibody
light chains or miRNA-150, respectively.
Conclusions: This is the first example of T-cell regulation
through systemic transit of exosome-like nanovesicles delivering
a chosen inhibitory miRNA to target effector T cells in an
antigen-specific manner by a surface coating of antibody light
chains