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PKC-ϴ is Dispensable for G-BMDC-Induced TCR-Independent Treg Proliferation

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thesis
posted on 31.10.2017 by Khaled Ahmed Alharshawi
GM-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 Immunology

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Committee Member

McLachlan, Alan Freitag, Nancy He, Bin Maker, Ajay V. Shahrara, Shiva

Submitted date

August 2017

Issue date

26/07/2017

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