The main goal of this program is to conduct a novel analysis of lymphocyte and innate lymphoid cell populations in human lymphoid and mucosal tissues in steady state and in organ transplantation, to elucidate novel aspects of human immune responses in the whole body that have not previously been explored. We will use two sources of human tissues for this program: deceased organ donors and transplant patients. Projects 1-3 will examine T, B and innate lymphoid cells (ILC) in multiple tissues obtained from . organ donors, and Project 4 will characterize lymphocyte and ILC populations in intestinal transplants. For all of the projects, the acquisition of human tissues is essential. The human tissue and sample acquisition core will be responsible for coordinating all ofthe personnel, institutional assurance, protocols and MTAs necessary to acquire and process human tissues, and distribute samples to all four projects. This core will function for all years of the project as it is essential to the entire program. This essential core will be divided into two parts based on the two main sources of human tissue samples. In the first part, the core will obtain and process multiple lymphoid and mucosal tissues from human organ donors. We have established the necessary protocols and collaborations with CUMC surgeons and the New York Organ Donor network (NYODN) to obtain from research-consented organ donors, tissues that are not used for life-saving transplantation. For this part of the core, we will coordinate the acquisition of multiple lymphoid tissues and mucosal tissues from organ donors whose next-of-kin have consented for use of tissues for research. The tissues will be processed in the laboratory and cell suspensions, whole tissues and tissue mounts will be distributed to all project laboratories (Projects 1-4). For the second part ofthe core, we will coordinate the acquisition of biopsy and peripheral blood samples from transplant patients. We will obtain biopsy and peripheral blood specimens from intestinal transplant patients who will be enrolled in studies related to Project 4. The personnel in this core will maintain IRB protocols for obtaining samples, enroll patients in this study, will work with the clinicians to obtain biopsy and blood samples as part of their clinical management, coordinate their distribution to Project 4 investigators for the characterization of T cell reconstitufion and alloreactivity, and to the CCTI Biobank for processing and storage.

Public Health Relevance

This novel research program in human immunology is centered upon a novel resource of human tissue acquisition from organ donors. The acquisition of multiple human lymphoid and mucosal tissues from organ donors in collaboration with the NYODN, and the enrollment and acquisition of samples from intestinal transplant patients will be organized and coordinated by this core for distribution to all project investigators.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI106697-01
Application #
8576984
Study Section
Special Emphasis Panel (ZAI1-QV-I (M1))
Project Start
2013-06-01
Project End
2018-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$256,830
Indirect Cost
$58,591
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Rosenfeld, Aaron M; Meng, Wenzhao; Luning Prak, Eline T et al. (2018) ImmuneDB, a Novel Tool for the Analysis, Storage, and Dissemination of Immune Repertoire Sequencing Data. Front Immunol 9:2107
Kumar, Brahma V; Connors, Thomas J; Farber, Donna L (2018) Human T Cell Development, Localization, and Function throughout Life. Immunity 48:202-213
Carpenter, D J; Granot, T; Matsuoka, N et al. (2018) Human immunology studies using organ donors: Impact of clinical variations on immune parameters in tissues and circulation. Am J Transplant 18:74-88
DeWolf, Susan; Grinshpun, Boris; Savage, Thomas et al. (2018) Quantifying size and diversity of the human T cell alloresponse. JCI Insight 3:
Senda, Takashi; Dogra, Pranay; Granot, Tomer et al. (2018) Microanatomical dissection of human intestinal T-cell immunity reveals site-specific changes in gut-associated lymphoid tissues over life. Mucosal Immunol :
Vander Heiden, Jason Anthony; Marquez, Susanna; Marthandan, Nishanth et al. (2018) AIRR Community Standardized Representations for Annotated Immune Repertoires. Front Immunol 9:2206
Chu, Coco; Moriyama, Saya; Li, Zhi et al. (2018) Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183. Cell Rep 23:3750-3758
Miron, Michelle; Kumar, Brahma V; Meng, Wenzhao et al. (2018) Human Lymph Nodes Maintain TCF-1hi Memory T Cells with High Functional Potential and Clonal Diversity throughout Life. J Immunol 201:2132-2140
Rosenfeld, Aaron M; Meng, Wenzhao; Chen, Dora Y et al. (2018) Computational Evaluation of B-Cell Clone Sizes in Bulk Populations. Front Immunol 9:1472
Fu, Jianing; Zuber, Julien; Martinez, Mercedes et al. (2018) Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool. Cell Stem Cell :

Showing the most recent 10 out of 63 publications