Project Details
Abstract
“Actively acquired tolerance” develops when in utero encounter with foreign antigens
during a period of immunological immaturity induces tolerance. Thus, self-nonself
discrimination is not an inherited property but rather gradually learned in the course of fetal or
early neonatal life until full development of immune system. Indeed, this logical, persuasive
yet novel premise has assisted in unraveling many core principles of immunology from the
earliest stages of lymphocyte differentiation to the principles of clinical autoimmunity as the
most solid pillars in immunology. Armed with this knowledge, in utero injection of
ovalbumin (OVA) was conducted in mice as an attempt to prenatally abolish allergic
responses. To our surprise, what is theoretically considered tolerogenic turned out to be
immunogenic. Mice prenatally exposed to OVA died of anaphylactic shock immediately after
intraperitoneal OVA injection in their postnatal life. The robust immunogenicity of fetal OVA
exposure, opposite to that intended from prenatal alloantigen exposure, is far beyond
expectation in modern immunology. Together with prenatal tolerance induction, the mice
committed foreign antigens to immunological memory whether an event of in utero exposure
is immunogenic or tolerogenic. Clearly, it’s the hallmark of adaptive immunity. As an
important link between innate and adaptive immunity, dendritic cells (DCs) are responsible
for capturing, processing and presenting antigens for the activation of naïve T-cells. This
drives a nonspecific phagocytic innate response into a more versatile means of defense that is
characterized by antigen-specific immune response and immunological memory to make
future responses against a specific antigen more efficient. An imprinting of sensitization to
OVA demands functioning of innate and adaptive immunity. How could this happen in the
absence of competent T-cells and DCs in a pre-immune fetus? Our pilot study revealed that
leukocytes of pre-immune murine fetuses were capable of capturing foreign antigens.
Tracking of foreign antigens in association with the cells that deal with foreign antigens may
help to demystify the phenomenon of in utero sensitization or tolerization, and further pave
the way to the cellular mechanisms of self-nonself discrimination.
Project IDs
Project ID:PC10301-0555
External Project ID:NSC102-2314-B182-026-MY3
External Project ID:NSC102-2314-B182-026-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/14 → 31/07/15 |
Keywords
- Tolerance
- Sensitization
- Antigen-capturing cell
- Fetus
- Cell tracking
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