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Immunological Response to DsDNA and Canine Papillomavirus-2 Infection in a Canine Model of X-linked Severe Combined Immunodeficiency

出版	University of California, Davis, 2013
ISBN	13034432449781303443244
URL	http://books.google.com.hk/books?id=jgnNoAEACAAJ&hl=&source=gbs_api

註釋X-linked severe combined immunodeficiency (XSCID) results from a genetic mutation within the common gamma chain ([gamma][c]), an essential component of the cytokine receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. XSCID patients are treated with bone marrow transplants (BMT) to restore their systemic immune function; however, these patients remain highly susceptible to papillomavirus infections. A similar observation has been made in a research colony of XSCID dogs. This dissertation was dedicated towards further understanding the role of keratinocytes and Langerhans cells in initiating an early immune response to canine papillomavirus in XSCID dogs. Since keratinocytes are the target cell for PV infections, we first characterized the antiviral immune response to a synthetic analog of viral dsDNA and then to canine papillomavirus. Our results demonstrated that although canine keratinocytes contained functional PRRs that recognized and responded to dsDNA and dsRNA ligands, they did not appear to recognize or initiate a similar response to canine papillomavirus. We then examined this antiviral immune response in keratinocytes from XSCID dogs and found that they responded similarly to normal keratinocytes. There was, however, a significantly altered baseline expression of antiviral cytokines and interferon responsive genes in epidermal explants from XSCID dogs. Finally, we determined using a polymerase chain reaction (PCR) assay that Langerhans cells remained recipient in origin and thus [gamma][c]-deficient in the XSCID dogs but they had comparable cell surface expression for MHCII, CD80, CD86, and ICAM-I to normal Langerhans cells. Taken together, these data suggests an altered baseline antiviral epidermal milieu in XSCID dogs that does not seem to be due to an inherent defect within the antiviral cytokine response of [gamma][c]-deficient keratinocytes.