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Temple University

1. Newman, Tiffanny Nicole. ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES.

Degree: PhD, 2011, Temple University

Microbiology and Immunology

The TULA-family consists of two proteins implicated in cellular regulation. TULA-1 is expressed in T-cells and is involved in apoptosis. TULA-2 is a ubiquitously expressed phosphatase that suppresses receptor-mediated signaling. T cells from mice lacking TULA-1 and 2 (double knockout, or dKO) are hypersensitive to TCR stimulation. This may be due to these proteins having a similar function working synergistically or dissimilar functions having a convergent effect. To understand functional interaction of these proteins we have characterized TULA-family knockout mice without and during an immune challenge. We show that CD4+ T cells of dKO mice have a characteristic CD45RB distribution, and that within the CD45RBlow subset effector/memory T cells are expanded only in dKO, but not in single knockouts (sKO) of either TULA-1 or TULA-2. However, CD4+ T cells of sKO and wild-type (WT) mice respond differently to TCR stimulation as seen using signaling and responses in vitro. To evaluate consequences of TULA deficiency in vivo, we utilized two mouse models of inflammatory bowel disease: TNBS-induced colitis and colitis induced by the adoptive transfer of CD45RBhigh CD4+ T cells. Studies utilizing TNBS indicate that deficiency of any TULA-family protein exacerbates TNBS-induced colitis. Likewise, dKO CD45RBhigh CD4+ T cells were significantly more colitogenic than cells from WT mice in the transfer model. Taken together, our data indicate that TULA-family proteins are key to the physiological regulation of T-cell reactivity that drives intestinal inflammation.

Temple University – Theses

Advisors/Committee Members: Tsygankov, Alexander, Henderson, Earl E., Buttaro, Bettina A., Safadi, Fayez F., Sanjay, Archana.

Subjects/Keywords: Immunology; autoimmune; inflammatory bowel disease; phosphatase; T cells; TULA-1; TULA-2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Newman, T. N. (2011). ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,210733

Chicago Manual of Style (16th Edition):

Newman, Tiffanny Nicole. “ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES.” 2011. Doctoral Dissertation, Temple University. Accessed September 24, 2020. http://digital.library.temple.edu/u?/p245801coll10,210733.

MLA Handbook (7th Edition):

Newman, Tiffanny Nicole. “ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES.” 2011. Web. 24 Sep 2020.

Vancouver:

Newman TN. ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES. [Internet] [Doctoral dissertation]. Temple University; 2011. [cited 2020 Sep 24]. Available from: http://digital.library.temple.edu/u?/p245801coll10,210733.

Council of Science Editors:

Newman TN. ROLE OF TULA-FAMILY PROTEINS IN T CELL DRIVEN RESPONSES. [Doctoral Dissertation]. Temple University; 2011. Available from: http://digital.library.temple.edu/u?/p245801coll10,210733

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