Exposure to NIMA-like alloantigens induces vigorous in vivo T cell responses in murine neonates (102.17)

Abstract

Abstract During early life, fetuses and neonates are exposed to allogeneic non-inherited maternal antigens (NIMA), through the passage of maternal cells and/or molecules across the placenta and in the breastmilk. Currently, it is thought that this early exposure results in the development of tolerance to NIMA. This is manifest in later life as an increased acceptance of grafts expressing the NIMA antigens. However, there also is evidence that exposure to NIMA during early life can lead to priming instead. In a murine model, we have shown that priming of neonates occurs when they are exposed to low doses of NIMA-like alloantigens. As these two possibilities, tolerance or priming, are extremely important for the outcome of transplantation, our lab has been engaged in studies to understand the in vivo responses of early life exposure to low doses of NIMA-like alloantigens. Following exposure, neonates developed both primary and memory cytotoxic responses to alloantigen. These responses were accompanied by vigorous Th1 and Th2 responses that exceeded the responses of adults similarly exposed. Overall, we conclude that exposure to low doses of NIMA-like alloantigens induces the development of robust cytotoxic and cytokine responses in neonates. This suggests that under specific conditions, early exposure to NIMA may lead to highly efficient immunological priming of all arms of T cell adaptive immunity, rather than tolerance. This work was supported by NIAID grant number R01 AI44923-02 (B.A.)