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Research at Mass General
The Benichou Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital is dedicated to:
Allorecognition is the ability of an organism to distinguish its own tissues from that of another. Our laboratory has developed a series of mouse models to study the different pathways of allorecognition (direct, indirect and semi-direct) by different T cell subsets (TH1, TH2, memory T cells and regulatory T cells), and the role of major histocompatability complex (MHC) cross-dressing and exosomes in the initiation and regulation of the immune responses leading to rejection or tolerance of allogeneic transplants.
In addition, we are investigating donor cell trafficking after transplantation and the roles of new blood and lymphatic vessels (neovascularization and lymphangiogenesis) in the immune response leading to allograft rejection. Based upon this knowledge, we are attempting to design novel strategies to achieve tolerance of allografts (same-species transplants) in mice using skin, heart and pancreatic mouse transplant models.
Additionally, we are currently evaluating the nature and mechanisms of action to different subsets of memory T cells in rejection and tolerance of allografts in transgenic and wild type mice.
Our laboratory is studying the immune mechanisms underlying tolerance of organ transplants in non-human primates. We have recently demonstrated that pre-existing alloreactive memory T cells (donor-reactive memory T cells present in the host prior to transplantation) prevent tolerance of allografts in primates via costimulation blockade (blocking the signal for T-cell activation) and hematopoietic chimerism. We are currently characterizing the precise nature of these memory T cells and investigating the mechanisms by which they impair tolerance. Based on this knowledge, we are currently designing clinically applicable strategies intended to suppress selectively these memory T cells and restore tolerance of kidney, heart and lung allografts in monkeys and patients.
Gilles Benichou, PhD, DSc
Senior Investigator/Head, Benichou Laboratory, Center for Transplantation Sciences (CTS)Immunologist, Massachusetts General HospitalAssociate Scientist, Department of Medicine, Boston Children’s HospitalAssociate Professor of Surgery and Immunology, Harvard Medical School
Gilles Benichou, PhD, DSc, is an associate professor of surgery and immunology at Harvard Medical School, senior immunologist at Mass General and head of the Benichou Laboratory in the Center for Transplantation Sciences (CTS) at Mass General. Dr. Benichou is a basic scientist who received his doctorate in Immunology in 1987 at the Pasteur Institute and the University of Science in Paris, France, for his studies of cell surface signaling by anti-major histocompatability complex (MHC) antibodies. He also received his Doctor of Science from the University of Science in Paris in 1997. Since 1987, his research has been focused on the mechanisms underlying the recognition of self versus non-self antigens by the immune system in cancer and transplantation.
Specifically, Dr. Benichou’s laboratory has shown the contribution of cryptic self-peptides to the induction of autoimmunity. Dominant and cryptic p53 peptides, which induce CD4+ T cell immune responses to tumors in mice and melanoma patients, have been identified and are currently being tested as cancer vaccines. In 1991, Dr. Benichou published the first article demonstrating the role of MHC-derived peptides in indirect alloreactivity during the course of allotransplant rejection.
Since then, Dr. Benichou’s laboratory has been studying the cellular and molecular mechanisms underlying direct and indirect types of allorecognition, including post-transplant autoimmunity in mouse models. In 2001, Dr. Benichou was recruited to the Department of Surgery at Mass General to develop clinical protocols for tolerance induction to allotransplants in primates. His most recent research at Mass General has led to the demonstration that the donor-specific memory T cells that present in primates pre-transplantation represent a formidable barrier to transplant tolerance induction.
Recently, Dr. Benichou’s studies revealed that primates displaying low frequencies of memory T cells against their donors could be successfully rendered tolerant of kidney allografts via the mixed chimerism protocol established at Mass General.
Georges Tocco, PhD
Mohamed Babiker, MDJose Marino, MDFelipe Naranjo, MD
William OrentAlex Hoslet
The Benichou Laboratory in the Center for Transplantation Sciences is leading the following research projects:
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