Defense Date

2012

Document Type

Thesis

Degree Name

Master of Science

Department

Microbiology & Immunology

First Advisor

Masoud Manjili

Abstract

The goal of hematopoietic stem cell transplantation (HSCT) is to induce graft-versus-tumor effect (GVT), which is the recognition of and response against tumor- associated antigens (TAAs) by donor immune cells to clear the recipient of residual tumor. A complication of HSCT as a treatment for hematologic malignancies is graft-versus-host disease (GVHD), which is the recognition and reactivity of donor immune cells against healthy tissues. As of now, the differentiation between GVHD and GVT effects has been a hindrance to the development of effective therapies against GVHD. Certain T cell clones may induce both GVHD and GVT effects, making targeted therapy of GVHD difficult. This project was aimed to uncover differences at a molecular level of the T cell recognition site that exist between patients with GVHD and those with GVHD-free survival following allogeneic HSCT. We found that there are inherent differences in the T cell receptor at a molecular level between patients experiencing GVHD and those that are GVHD-free, suggesting the ability of T cells to distinguish tumor cells from self cells. In addition, the intention was to reveal differences in proportions of engrafted donor T cells and stem cells and the effects of these proportions on the severity, outcome, and prognosis of GVHD. We additionally found that a lower proportion of stem cells to T cells was associated with the trend of GVHD, while a higher frequency of T cells engrafted into host may indicate resistance to treatment and a poor prognosis. These data suggest that allogeneic HSCT may be improved by optimizing the proportion of T cells to stem cells in the transplant as well as developing targeted therapy against GVHD-associated T cell clones while rescuing GVT-associated T cell clones.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

May 2012

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