eprintid: 7144 rev_number: 4 userid: 6 dir: disk0/00/00/71/44 datestamp: 2011-11-10 19:37:13 lastmod: 2016-11-15 13:40:13 status_changed: 2011-11-10 19:37:13 type: thesis_degree metadata_visibility: show contact_email: akhst7@imap.pitt.edu item_issues_count: 0 eprint_status: archive creators_name: Hoji, Aki creators_email: akhst7@imap.pitt.edu title: CHARACTERIZATION OF VIRUS-SPECIFIC CD8+ T CELL DIFFERENTIATION ispublished: unpub divisions: sch_gsph_infectiousdiseasesmicrobiology full_text_status: public keywords: AIDS; CD8+ T cells; Flow Cytometry; HIV; Immunology; Differentiation; Immunophenotype abstract: Virus-specific memory CD8+ T cells play a prominent role in protection of a host from recurring and persistent virus infection. It is known that memory CD8+ T cells undergo a series of differentiation stages to become fully matured effector cells. There are several important aspects of the current CD8+T cell memory phenotype model that need to be more thoroughly defined. In specific aim 1, it was hypothesized that CD27+CD28+ undifferentiated CD8+ memory T cells specific for non-persistent virus influenza A (FluA) would have phenotypic markers associated with more differentiated (effector) phenotypes. Results showed that in spite of the phenotypic enrichment of FluA-specific memory CD8+ T cells in the undifferentiated stage, they displayed effector markers indicative of late stage differentiated effector cells. In specific aim 2, it was further hypothesized that the most undifferentiated CD62L+ central memory CD8+T cells would have the effector function including immediate cytoplasmic production of gamma-IFN upon antigenic-stimulation. Results showed that CD62L+ CD8+ T cells are capable of immediate gamma IFN production after antigen-specific stimulation in the presence of the CD62 sheddase inhibitor, GM6001, highlighting the need to re-evaluate the defining markers of virus-specific central memory CD8+ cells and/or their functions. In specific aim 3, this dissertation tests the hypothesis that memory-effector differentiation of HIV-1-specific memory CD8+ T cells is impaired during the course of persistent HIV-1 infection. Detailed comparison of CD27 and CD57 co-expression on HIV-1-specific CD8+ T cells showed that these cells had a significantly lower proportion of the CD27-CD57high effector subset. Moreover, these cells did not display progression from CD27+CD57- (immature memory), through CD27lowCD57low (transitional memory-effector) to CD27-CD57high (effector subset) that was seen in well differentiated EBV-specific CD8+ T cells and was common in CMV-specific CD8+ T cells. These observations suggest that the normal course of HIV-1-specific CD8+ T cell memory-effector differentiation is impaired during the course of persistent HIV-1 infection. Elucidation of memory-effector differentiation of virus-specific CD8+ T cells has significant public health implications. Understanding the impairment of memory-effector differentiation of HIV-1-specific CD8+ T cells, for instance, will greatly facilitate a design of effective vaccine against progressive HIV-1 infection. date: 2005-06-09 date_type: completed institution: University of Pittsburgh refereed: TRUE etdcommittee_type: committee_chair etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_name: Rinaldo, Charles R etdcommittee_name: Trucco, Massimo M etdcommittee_name: Finn, Olivera J etdcommittee_name: Gupta, Phalguni etdcommittee_name: Barratt-Boyes, Simon M etdcommittee_email: rinaldo@pitt.edu etdcommittee_email: mnt@pitt.edu etdcommittee_email: ojfinn@pitt.edu etdcommittee_email: pgupta1@pitt.edu etdcommittee_email: smbb@pitt.edu etdcommittee_id: RINALDO etdcommittee_id: MNT etdcommittee_id: OJFINN etdcommittee_id: PGUPTA1 etdcommittee_id: SMBB etd_defense_date: 2005-03-29 etd_approval_date: 2005-06-09 etd_submission_date: 2005-04-14 etd_access_restriction: immediate etd_patent_pending: FALSE assigned_doi: doi:10.5195/pitt.etd.2011.7144 thesis_type: dissertation degree: PhD committee: Charles R. Rinaldo, Jr. (rinaldo@pitt.edu) - Committee Chair committee: Massimo M. Trucco (mnt@pitt.edu) - Committee Member committee: Olivera J. Finn (ojfinn@pitt.edu) - Committee Member committee: Phalguni Gupta (pgupta1@pitt.edu) - Committee Member committee: Simon M. Barratt-Boyes (smbb@pitt.edu) - Committee Member etdurn: etd-04142005-153607 other_id: http://etd.library.pitt.edu/ETD/available/etd-04142005-153607/ other_id: etd-04142005-153607 citation: Hoji, Aki (2005) CHARACTERIZATION OF VIRUS-SPECIFIC CD8+ T CELL DIFFERENTIATION. Doctoral Dissertation, University of Pittsburgh. (Unpublished) document_url: http://d-scholarship-dev.library.pitt.edu/7144/1/Ahoji2005.pdf