Submitted August 10, 2007
Accepted May 20, 2008
Murine neonates develop vigorous in vivo cytotoxic and Th1/Th2 responses upon exposure to low doses of NIMA-like alloantigens
Shannon J Opiela, Robert B Levy, and Becky Adkins*
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United States
* Corresponding author; email: radkins{at}med.miami.edu.
Early life exposure to non-inherited maternal antigens (NIMA) may occur via transplacental transfer and/or breastmilk. There are indications that early life exposure to NIMA may lead to lifelong tolerance. However, there is mounting evidence that exposure to NIMA may also lead to immunological priming. Understanding how these different responses arise could be critical in transplantation with donor cells expressing NIMA. We recently reported that murine neonates transplanted with low doses of NIMA-like alloantigens develop vigorous memory cytotoxic responses, as assessed by in vitro assays. Here, we demonstrate that robust allospecific cytotoxicity is also manifest in vivo. Importantly, at low doses, NIMA-expressing cells induced the development of in vivo cytotoxicity during the neonatal period. NIMA-exposed neonates also developed vigorous primary and memory allospecific Th1/Th2 responses which exceeded the responses of adults. Overall, we conclude that exposure to low doses of NIMA-like alloantigens induces robust in vivo cytotoxic and Th1/Th2 responses in neonates. These findings suggest that early exposure to low levels of NIMA may lead to long term immunological priming of all arms of T cell adaptive immunity, rather than tolerance.
