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CHARACTERIZATION OF VIRUS-SPECIFIC CD8+ T CELL DIFFERENTIATION

Hoji, Aki (2005) CHARACTERIZATION OF VIRUS-SPECIFIC CD8+ T CELL DIFFERENTIATION. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hoji, Akiakhst7@imap.pitt.edu
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairRinaldo, Charles Rrinaldo@pitt.eduRINALDO
Committee MemberTrucco, Massimo Mmnt@pitt.eduMNT
Committee MemberFinn, Olivera Jojfinn@pitt.eduOJFINN
Committee MemberGupta, Phalgunipgupta1@pitt.eduPGUPTA1
Committee MemberBarratt-Boyes, Simon Msmbb@pitt.eduSMBB
Date: 9 June 2005
Date Type: Completion
Defense Date: 29 March 2005
Approval Date: 9 June 2005
Submission Date: 14 April 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: AIDS; CD8+ T cells; Flow Cytometry; HIV; Immunology; Differentiation; Immunophenotype
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04142005-153607/, etd-04142005-153607
Date Deposited: 10 Nov 2011 19:37
Last Modified: 15 Nov 2016 13:40
URI: http://d-scholarship.pitt.edu/id/eprint/7144

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