Title |
T Cell Reconstitution After Allogeneic SCT
|
Institution |
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE, CORAL GABLES, FL
|
Principal Investigator |
Komanduri, Krishna
|
NCI Program Director |
Jason Yovandich
|
Cancer Activity |
Biological Resources Branch
|
Division |
DCTD
|
Funded Amount |
$257,865
|
Project Dates |
09/28/2005 - 05/31/2010
|
Fiscal Year |
2009
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
Organ Transplantation Research (100.0%)
|
N/A
|
Research Type |
Systemic Therapies - Clinical Applications
|
Abstract |
DESCRIPTION (provided by applicant): Allogeneic stem cell transplantation (SCT) remains an important therapeutic modality for a wide variety of malignant disease and is curative for many individuals who may not otherwise survive following treatment with chemotherapy alone. Infection remains a major cause of morbidity and mortality after SCT, and is largely attributable to impaired T cell immune reconstitution. To develop approaches to actively intervene to improve T cell reconstitution, it is crucial for us to systematically identify the factors governing T cell homeostasis after SCT. We hypothesize that the recipient thymus contributes to the recovery of naive and functional antigen-specific T cells after SCT, and that impaired thymic function results in delays in the recovery of these T cell subsets. We further hypothesize that the transfer of memory T cells in the donor graft may lead to more rapid T cell recovery after SCT, but that the transfer of activated memory T cells may facilitate the development of graft-versus-host disease in recipients. We hypothesize that GVHD impairs thymopoiesis in recipients and decreases the production of cytokines important in T cell homeostasis, and that immunosuppressive therapy for GVHD suppresses thymopoiesis and induces anergy in virus-specific memory CD8+ T cells. These hypotheses will be tested in the following Specific Aims: 1. To determine the role of the recipient thymus in the recovery of a diverse and functional T cell repertoire after stem cell transplantation. 2. To define how the transfer of memory T cells in the donor graft influences antigen-specific T cell recovery and GVHD in SCT recipients. 3. To determine whether GVHD and its treatment impair thymopoiesis and the function of antigen-specific memory T cells in SCT recipients. |