2 options
Role of IL-27 and TCR Stimulation in Inhibitory Receptor Expression / Jonathan Howard DeLong.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- DeLong, Jonathan Howard, author.
- Language:
- English
- Subjects (All):
- Immunology.
- Immunology--Penn dissertations.
- Penn dissertations--Immunology.
- Local Subjects:
- Immunology.
- Immunology--Penn dissertations.
- Penn dissertations--Immunology.
- Genre:
- Academic theses.
- Physical Description:
- 1 online resource (136 pages)
- Contained In:
- Dissertations Abstracts International 80-07B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2018.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- The adaptive immune response is necessary for control of pathogen burden in a wide range of infections. However, in the absence of active regulatory mechanisms, this protective response can lead to immune pathology. The cytokine interleukin (IL)-27 is required for control of exaggerated immune responses during toxoplasmosis and other infections and autoimmune settings. Multiple regulatory pathways have been found to be controlled by IL-27. However, there are gaps in our knowledge of the mechanisms by which IL-27 limits T cell responses. The present work focuses on the ability of IL-27 to promote expression of inhibitory receptors on T cells. The studies presented here establish that TCR and cytokines have distinct and complementary roles in promoting inhibitory receptor expression. In vitro, IL-27, type I IFN, and IFN-g induced expression of PD-L1 and Sca-1 on naive murine CD4+ and CD8+ T cells in the absence of TCR stimulation. TCR stimulation induced expression of multiple inhibitory receptors and IL- 27 combined synergistically with TCR stimulation to further upregulate Ly6C, LAG-3, CTLA-4, TIGIT and TIM-3. This IL-27-mediated inhibitory expression was STAT1- dependent. The response to TCR stimulation was graded and thus a stronger TCR stimulus resulted in greater inhibitory receptor expression. In vivo, during infection with Toxoplasma gondii, IL-27 was required for full expression of Ly6C, PD-L1, LAG-3, CTLA-4, and TIGIT by parasite-specific T cells in the lung, a local site of infection, but not in the spleen. STAT1 was also required for full expression of LAG-3, CTLA-4, and TIGIT at local sites of infection. Taken together, these studies suggest a model in which inhibitory receptor expression on T cells is a graded regulatory pathway that is upregulated by exposure to increasing levels of TCR stimulation and cytokines present at sites of inflammation.
- Notes:
- Source: Dissertations Abstracts International, Volume: 80-07, Section: B.
- Publisher info.: Dissertation/Thesis.
- Advisors: Hunter, Christopher A.; Committee members: Michael Cancro; Taku Kambayashi; Paula Oliver; Andrew Wells; E. John Wherry.
- Department: Immunology.
- Ph.D. University of Pennsylvania 2018.
- Local Notes:
- School code: 0175
- ISBN:
- 9780438766952
- Access Restriction:
- Restricted for use by site license.
- This item must not be sold to any third party vendors.
The Penn Libraries is committed to describing library materials using current, accurate, and responsible language. If you discover outdated or inaccurate language, please fill out this feedback form to report it and suggest alternative language.