Date of Award

January 2013

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Michael Girardi

Subject Area(s)

Medicine

Abstract

Extracorporeal photopheresis (ECP) in the treatment of cutaneous T-cell lymphoma, GVHD and autoimmune conditions continues to spur the question of how ECP is capable of inducing immunogenicity and tolerance. We previously demonstrated that ECP treatment leads to large-scale conversion of peripheral blood monocytes into functionally competent leukocytes with dendritic cell phenotypes, which may play key roles in the immunomodulatory capabilities of ECP. To characterize this population of cells on a molecular level, we assessed for differential surface expression of selected gene-products on monocytes after treatment with a model-ECP apparatus. Five gene-products (CXCL16, SIRPa, ICAM1, TNFR1, PLAUR) showed significant increases in surface expression after model-ECP treatment as compared to PBMC (p <0.01 for all). To identify transcription factors (TFs) expressed by ECP-treated monocytes but not peripheral blood monocytes, rtPCR was performed. Interactions with platelets during ECP passage was also assessed by using model-ECP plates coated with low- and high-density platelets. Seven TFs demonstrated increases in mRNA after passage through the model-ECP plate (ΔRQ range 1.35- 6.78). Increased platelet density induced directional changes in expression (RQ < 0.5) for VDR, NFkB2, CDKN1A and BCL3. In summary, passage through the ECP plate apparatus caused activation of novel surface molecules and transcription factors that define and characterize a unique subset of "physiologically-induced" DCs.

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