Gilles Benichou, Ph.D.
Transplant Surgery, Mass General Research Institute
Associate Professor of Surgery
Harvard Medical School
Harvard Stem Cell Institute
The Benichou Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital is dedicated to:
- Elucidating the mechanisms underlying the recognition of donor antigens by recipient lymphocytes after transplantation of allogeneic (from the same species) organs and tissues
- Characterizing the nature of the cells and their mechanisms of action involved in the rejection or tolerance of allogeneic transplants
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.