?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F16473%2F&rft.title=Cytokine+and+Chemokine+Responses+in+Human+Herpesvirus+8+Infection+of+Monocyte+Derived+Dendritic+Cells+and+B+Lymphocytes&rft.creator=Knowlton%2C+Emilee+R.&rft.description=Human+herpesvirus-8+induces+a+wide+range+of+inflammatory+immune+mediators+known+to+contribute+to+its+associated+cancer%2C+Kaposi%E2%80%99s+Sarcoma+(KS).++Soluble+immune+mediators%2C+such+as+cytokines%2C+chemokines+and+growth+factors+produced+during+HHV-8+infection+have+been+associated+with+tumor-cell+proliferation%2C+angiogenesis+and+vascular+permeability.+We+sought+to+determine+immune+mediator+production+by+two+antigen+presenting+cells+(APC)+that+are+susceptible+to+HHV-8+infection%2C+i.e.%2C+monocyte+derived+Dendritic+cells+(MDDC)+and+B+lymphocytes.+%0D%0A++++++Dendritic+cells+abundantly+express+the+HHV-8+receptor%2C+type+II+C-type+lectin%2C+DC-specific+ICAM-3+grabbing+nonintegrin+(DC-SIGN)+resulting+in+viral+entry%2C+whereas+only+a+small+percentage+of+activated+B+cells+express+DC-SIGN+in+vitro.++Despite+this%2C+HHV-8+infection+of+MDDC+results+in+an+abortive+replicative+cycle%2C+whereas+full-lytic+cycle+replication+occurs+in+the+B+cells.++I+hypothesized+that+immune+mediators+produced+by+HHV-8+infected+APC+are+unique+between+cell+types+and+that+HHV-8+infects+a+subset+of+B+cells+and+initiates+cytokine+and+chemokine+production+that+contributes+to+HHV-8+replication%2C+viral+dissemination+and+initiation+of+KS+and+HHV-8+lymphomas.%0D%0A++++++I+used+a+cytometric+bead+array+to+determine+cytokine+and+chemokine+production+in+B+cells+and+MDDC%2C+as+well+as+qRT-PCR%2C+TCID50+assay+and+flow+cytometry+to+determine+HHV-8+replication+in+B+cells.++I+identified+significant+differences+in+the+quality+and+quantity+of+cytokine+and+chemokine+profiles+of+HHV-8+infected+APC.++MDDC+produced+significant+levels+of+MCP-1%2C+MIP-1%CE%B1%2C+MIP-1%CE%B2%2C+RANTES%2C+IP-10+and+IL-10%2C+while+B+cells+produced+significant+levels+of+MIP-1%CE%B1%2C+MIP-1%CE%B2%2C+IL-6%2C+TNF-%CE%B1+and+IL-8.++HHV-8+lytic+replication+in+B+cells+resulted+in+polyfunctional+immune+mediator+activity+that+may+contribute+to+viral+replication+and+proliferation+of+target+cell+populations+in+HHV-8+related+cancers.++The+importance+of+this+work+was+demonstrated+by+the+detection+of+B+cell-produced+cytokines+and+chemokines+in+HHV-8%2FHIV+co-infected+individuals+who+developed+KS.++This+is+the+first+extensive%2C+multiparameter%2C+longitudinal+study+of+HHV-8+infection+of+B+cells+and+immune+mediators+in+development+of+KS.++This+study+provides+novel+targets+for+vaccine+development+and+treatment+options+for+KS%2C+which+could+have+great+implications+on+Public+Health.&rft.date=2013-01-29&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fvnd.ms-excel&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F16473%2F4%2FE.Knowlton_Microarray_Data.xlsx&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F16473%2F5%2FEKnowlton_Dissertation_12.14.12.pdf&rft.identifier=++Knowlton%2C+Emilee+R.++(2013)+Cytokine+and+Chemokine+Responses+in+Human+Herpesvirus+8+Infection+of+Monocyte+Derived+Dendritic+Cells+and+B+Lymphocytes.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++