ALHARSHAWI-DISSERTATION-2017.pdf (3.93 MB)
PKC-ϴ is Dispensable for G-BMDC-Induced TCR-Independent Treg Proliferation
thesis
posted on 2017-10-31, 00:00 authored by Khaled Ahmed AlharshawiGM-CSF-induced bone marrow derived dendritic cells (G-BMDCs) have been shown by our lab to be able to selectively cause Treg proliferation when co-cultured with CD4+ T cells. This Treg proliferation was shown to be TCR-independent but OX40L/OX40-dependent. In this thesis work we studied the signaling involved in the G-BMDC-induced Treg proliferation. Firstly, we confirmed the critical role of OX40L/OX40 signaling in Treg expansion by using CD4+ T cells from OX40 deficient mice, which failed to proliferate significantly. Because PKC-ϴ was shown to play an important role downstream of OX40 signaling in conventional T cells in the absence of TCR stimulation, we investigated the role of PKC-ϴ in G-BMDC-induced Treg expansion. Interestingly, CD4+ T cells from PKC-ϴ deficient mice, upon co-culture with WT G-BMDCs, showed impaired Treg proliferation. However, supplementation of the co-culture with exogenous IL-2 restored Treg proliferation, suggesting that G-BMDC-induced Treg proliferation per se was PKC-ϴ-independent. Our data further suggested that PKC-ϴ is likely required for optimum IL-2 production by T effector cells. Finally, our data suggested that OX40 mediated downstream signaling in Tregs likely involves TRAF1. Therefore, OX40L mediated TCR-independent Treg proliferation could be an effective means of selectively expanding Treg as a potential therapeutic for autoimmune disease including T1D.
History
Advisor
Prabhakar, Bellur S.Chair
Prabhakar, Bellur S.Department
Microbiology and ImmunologyDegree Grantor
University of Illinois at ChicagoDegree Level
- Doctoral
Committee Member
McLachlan, Alan Freitag, Nancy He, Bin Maker, Ajay V. Shahrara, ShivaSubmitted date
August 2017Issue date
2017-07-26Usage metrics
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