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.

Available for download on Tuesday, April 24, 2018

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