Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Regulation of MUC1-specific immunity by CD4+ T cells

Turner, Michael Stuart (2005) Regulation of MUC1-specific immunity by CD4+ T cells. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (1MB) | Preview


MUC1 is a large glycoprotein that is expressed on ductal epithelial cells and also the majority of epithelial adenocarcinomas. Dysregulated expression of aberrantly glycoslyated MUC1 in carcinomas allows tumor-specific recognition of MUC1-derived epitopes by antibodies and T lymphocytes. However, despite the ability of CTL to specifically recognize and kill MUC1+ tumor cells, immune responses in cancer patients fail to prevent tumor progression. The failure of patients' immune systems to eradicate MUC1+ tumors has been linked with their inability to mount MUC1-specific helper T cell responses.Here we show that CD4+ T cells play a central role in both the enhancement and suppression of MUC1-specific immune responses. Using MUC1-Tg mice as a model for tolerance to self-expressed MUC1, we show that MUC1-specific regulatory T cells (Tregs) respond to stimulation with MUC1 in the absence of a CD4+ T helper response. The Treg:Th imbalance in MUC1-Tg mice causes the suppression of MUC1-specific immunity. This suppression can be overcome by providing functional Th cells from WT mice. To focus our studies on MUC1-specific CD4+ T cells, we created a TCR-transgenic mouse whose CD4+ T cells are specific for an MHC Class II-restricted epitope derived from unglycosylated MUC1. Using these mice, we have confirmed that adoptive transfer of MUC1-specific CD4+ T replaces the MUC1-specific T cell help that is missing in MUC1-Tg mice and restores their ability to respond to MUC1 vaccines. This work shows that the generation of CD4 helper T cell responses is critical to establishing effective immunity to MUC1+ cancers.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Turner, Michael
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFinn, Olivera Jojfinn@pitt.eduOJFINN
Committee MemberZeevi, Adriana
Committee MemberHendricks, Robert L
Committee MemberPlevy, Scott E
Committee MemberSmithgall, Thomas E
Date: 14 December 2005
Date Type: Completion
Defense Date: 11 November 2005
Approval Date: 14 December 2005
Submission Date: 12 December 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Immunology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: cancer; transgenic; Tregs; vaccine
Other ID:, etd-12122005-154355
Date Deposited: 10 Nov 2011 20:10
Last Modified: 15 Nov 2016 13:54


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item