Semester

Summer

Date of Graduation

2005

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

Solveig G. Ericson.

Abstract

Much has yet to be understood about the role of specific families of T lymphocytes in the post human hematopoietic stem cell (HSC) transplant environment. Prior work in the field has identified T cells based upon the expression of their T cell receptor beta variable regions (TCRBV). In this investigation we developed a comprehensive panel of oligonucleotides that can be used to determine the expression of all 91 alleles of the human TCRBV regions using real time PCR technology. Application of this technology to peripheral blood samples collected weekly from allogeneic peripheral blood stem cell transplant patients yielded the following findings: (1) specific TCRBV families are associated with the reactivation of cytomegalovirus (CMV) post HSC transplant with many of these same TCRBV families also being associated with the occurrence of GVHD, (2) the TCRBV repertoire engrafts in the recipient with a profile more similar to that found in the donor as opposed to that found in the recipient prior to transplant, and (3) the similar immunosuppressive agents, cyclosporin A (CSA) and tacrolimus (FK506), differentially alter the TCRBV repertoire with their administration, a difference which can not be attributed to a divergent inhibition of calcineurin or IL-2 production by CSA or FK506.

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