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INFLUENCE OF NON-INHERITED MATERNAL ANTIGENS: NEW INSIGHTS USING TRANSGENIC MODELS.
Yoshinobu Akiyama, MD, Stephane Caucheteux, PhD, Yoshiko Iwamoto, BS, Colette Kanellopoulos, PhD and Gilles Benichou, PhD. Boston MA, USA, MGH/Harvard med School, 02114, Surgery and Paris Paris, France, Institut J. Monod, CNRS, 75005, Reproduction Biology.

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We have studied the influence of non-inherited maternal antigen (NIMA) on the alloimmune response and allograft rejection using a mouse transgenic model. To test this, CBK transgenic (CBA mice expressing Kb MHC class I transgene) mice were used as donors in skin and heart transplantation experiments. Offspring of BM3.3 Kb T cell receptor (TCR) transgenic mice and F1female from CBA and CBK were used as NIMA (Kb exposed but not expressing Kb) and IMA (inherited Kb maternal antigen) recipients. Following transplantation, graft survival was monitored as well as alloimmune response using an ELISPOT assay. All IMA-exposed mice accepted either skin or heart allografts and displayed no alloreactivity to Kb+ cells. In contrast, all the mice, which had no exposure to Kb (offspring from BM3.3 Kb TCR Tg mice and CBA females), rejected their grafts within 12 days post transplantation and exhibited potent alloresponses to Kb+ allogeneic cells. Most importantly, mice, which had been exposed to NIMA, had prolonged survival of skin (27 days) and heart transplants (> 58 days). This was associated with a significant reduction of the frequency of activated alloreactive T cells producing type 1 (gIFN and IL-2) cytokines. No deletion of anti-Kb T cells was found in mice exposed to NIMA. In turn, the NIMA effect was abrogated by in vivo treatment with anti-CD4 antibodies. This study, provides the first demonstration of the tolerogenic effects of NIMA on alloimmunity and allograft rejection in a transgenic model.
Supported by a NATO Science program collaborative grant