to the CCTI's Dr. Adam GriesemerWednesday, February 4, 2015
The Irving Institute for Clinical and Translational Research awarded 16 faculty members Irving Institute/Clinical Trials Office Pilot Awards, which provide junior faculty with funds to conduct pilot studies needed to attract future independent funding and our own Dr. Adam Griesemer has been chosen as one of the 2014 awardees!
Thursday, January 29, 2015
Nature Biotech highlighted our paper on twitter: https://twitter.com/NatureBiotech/status/560574101128237056
"Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients"in Science Translational MedicineWednesday, January 28, 2015
When a patient receives a transplant, a unique population of T lymphocytes emerges to reject the foreign organ. Immunosuppressive medication is therefore necessary to prevent rejection and protect the transplanted kidney. Previously, it had not been possible in humans to identify these specific T cells due to their vast number and diversity; furthermore, this population is unpredictable and distinct for each transplant patient and his or her organ donor. In this paper, we describe a new technique to identify these thousands of T cells before the time of kidney transplantation and then track them over time after transplant circulating in peripheral blood. We used this technique to study six kidney transplant recipients to investigate in a new way what happens to these cells when patients have different clinical outcomes. Some of the patients studied were part of a unique cohort who received combined kidney and bone marrow transplants from the same donor in order to induce tolerance and accept their grafts without life-long immunosuppressive medication. Our T cell tracking analysis provided a deeper understanding of the mechanism of tolerance in these patients. This new technique provides a window into the fate of these donor-specific T cells and has potential as a possible biomarker for predicting and identifying rejection and tolerance in different types of transplant patients.
Project: The Immune Privilege of the Hematopoietic Stem Cell NicheMonday, January 26, 2015
Dr. Joji Fujisaki, MD. PhD, was recently awarded a prestigious 2015 Schaefer Research Scholar Award by Columbia University, the selection for which is based upon “outstanding merit for the proposed research and as carried out in the past year; along with the likelihood of outstanding future research. See this link for more information about Dr. Fujisaki's research.
Dr. Donna Farber, et alThursday, November 6, 2014
Mechanisms for human memory T cell differentiation and maintenance have largely been inferred from studies of peripheral blood, though the majority of T cells are found in lymphoid and mucosal sites. We present here a multidimensional, quantitative analysis of human T cell compartmentalization and maintenance over six decades of life in blood, lymphoid, and mucosal tissues obtained from 56 individual organ donors. Our results reveal that the distribution and tissue residence of naive, central, and effector memory, and terminal effector subsets is contingent on both their differentiation state and tissue localization. Moreover, T cell homeostasis driven by cytokine or TCR-mediated signals is different in CD4+ or CD8+ T cell lineages, varies with their differentiation stage and tissue localization, and cannot be inferred from blood. Our data provide an unprecedented spatial and temporal map of human T cell compartmentalization and maintenance, supporting distinct pathways for human T cell fate determination and homeostasis. Click here for the full paper published in the most recent issue of Cell.
Dr. Adam Griesemer receives grant from the Irving Institute/Clinical Trials Office (CTO) Pilot Award for 2014Friday, October 10, 2014
Clinical Trials Office Pilot Award from the Irving Institute for Translational Research for a grant entitled: "Combined liver and bone marrow transplantation for the induction of tolerance to liver allografts". The goal of this study is to induce tolerance to liver allografts in a preclinical cynomolgus monkey model through the co-transplantation of donor bone marrow and an enhanced immunological conditioning regimen.
Thursday, May 15, 2014
New York-Presbyterian/Columbia University Medical Center has opened the Irving Bone Marrow Transplant Unit, a state-of-the-art facility for comprehensive bone marrow transplant (BMT) care. The new unit features 18 inpatient rooms, a high-tech nurses station for individual patient monitoring, and a specialized airflow system to help protect patients with weakened immune systems. The unit is supported by a $20 million gift from Herbert and Florence Irving. Read the entire story here.
American Journal of Transplantation: Official Journal of the American Society of Transplantation and the American Society of Transplant SurgeonsFriday, December 13, 2013
Avoidance of long-term immunosuppression is a desired goal in organ transplantation. Mixed chimerism offers a promising approach to tolerance induction, and we have aimed to develop low-toxicity, nonimmunodepleting approaches to achieve this outcome. In a mouse model achieving fully MHC-mismatched allogeneic bone marrow engraftment with minimal conditioning (3 Gy total body irradiation followed by anti-CD154 and T cell-depleted allogeneic bone marrow cells), CD4 T cells in the recipient are required to promote tolerance of preexisting alloreactive recipient CD8 T cells and thereby permit chimerism induction. We now demonstrate that mice devoid of CD4 T cells and NK cells reject MHC Class I-deficient and Class I/Class II-deficient marrow in a CD8 T cell-dependent manner. This rejection is specific for donor alloantigens, since recipient hematopoiesis is not affected by donor marrow rejection and MHC Class I-deficient bone marrow that is syngeneic to the recipient is not rejected. Recipient CD8 T cells are activated and develop cytotoxicity against MHC Class I-deficient donor cells in association with rejection. These data implicate a novel CD8 T cell-dependent bone marrow rejection pathway, wherein recipient CD8 T cells indirectly activated by donor alloantigens promote direct killing, in a T cell receptor-independent manner, of Class I-deficient donor cells.
Distribution and Compartmentalization of Human Circulating and Tissue-Resident Memory T Cell SubsetsImmunity, December 2012Thursday, December 20, 2012
Knowledge of human T cells derives chiefly from studies of peripheral blood, whereas their distribution and function in tissues remains largely unknown. Here, we present a unique analysis of human T cells in lymphoid and mucosal tissues obtained from individual organ donors, revealing tissue-intrinsic compartmentalization of naive, effector, and memory subsets conserved between diverse individuals. Effector memory CD4+ T cells producing IL-2 predominated in mucosal tissues and accumulated as central memory subsets in lymphoid tissue, whereas CD8+ T cells were maintained as naive subsets in lymphoid tissues and IFN-γ-producing effector memory CD8+ T cells in mucosal sites. The T cell activation marker CD69 was constitutively expressed by memory T cells in all tissues, distinguishing them from circulating subsets, with mucosal memory T cells exhibiting additional distinct phenotypic and functional properties. Our results provide an assessment of human T cell compartmentalization as a new baseline for understanding human adaptive immunity.
Dr. Sykes speaks to WNYC's "The Takeaway"Thursday, September 27, 2012