Date of Award
5-10-2017
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Biology
First Advisor
Yuan Liu
Second Advisor
William Walthall
Third Advisor
Deborah Baro
Abstract
Tumor-induced myeloid derived suppressive cells (MDSC) have been reported to inhibit T cell responses. In our study MDSC isolated from tumor bearing mice showed potent inhibition of T-cell proliferation. However, surprisingly we observed that freshly isolated MDSC from the bone marrow of tumor bearing mice do not constitutively express arginase-1 until after exposure to T-cell proliferation. The aim of this study is to determine the mechanism by which arginase-1 is induced in MDSC following exposure to a proliferative T cell environment. We showed that treatment of MDSC with culture supernatant isolated from T cells activated with CD3/CD28 antibodies successfully induced arginase-1 expression and this process is independent of IL-10 and IFNγ. This suggested that arginase-1 induction in MDSC can occur independently of cell-cell contact. Interestingly IL-2, ConA or PMA activated T-cell supernatant as well as supernatant from multiple cancer cell lines failed to induce arginase-1 in MDSC. We also showed that M-MDSC expressed higher levels of arginase-1 than G-MDSC after co-culture with CD3/CD28 activated T cells as well as its supernatant. In addition, other bone marrow cells have shown the potential to express arginase-1 following exposure to the same conditions. For example, we observed that healthy Ly6C+ monocytes but not mature granulocytes successfully expressed arginase-1.These data demonstrated that T cells activated through stimulation of TCR but not other means of activation induced arginase-1 enzyme expression.
DOI
https://doi.org/10.57709/10064920
Recommended Citation
Abdelbaky Abdelaal, Ahmed, "Induction Of Arginase-1 In MDSC Requires Exposure to CD3/CD28 Activated T Cells." Thesis, Georgia State University, 2017.
doi: https://doi.org/10.57709/10064920