Tracking of Foreign Antigens to Which the Pre-Immune Fetus Is Exposed

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


“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
Effective start/end date01/08/1431/07/15


  • Tolerance
  • Sensitization
  • Antigen-capturing cell
  • Fetus
  • Cell tracking


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