Date of Award

August 2018

Degree Type

Thesis

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Douglas Steeber

Committee Members

Douglas Steeber, Julie Oliver, Heather Owen

Keywords

Immune response, PI3K Pathway, T cell migration, ZAP70 Signaling

Abstract

ABSTRACT

DIFFERENTIAL MIGRATION OF CD4+ AND CD8+ T CELLS DURING AN IMMUNE RESPONSE

by

Jacob Parrott

The University of Wisconsin-Milwaukee, 2018

Under the Supervision of Professor Douglas Steeber

Lymphocyte migration is critical for recognizing pathogenic challenges in a timely manner and generating effective, rapid immune responses. Lymphocyte numbers in secondary lymphoid tissues such as lymph nodes are rapidly and dramatically increased during an immune response. Lymphocytes use specific adhesion molecules and intracellular signaling cascades to migrate and enter secondary lymphoid tissues under resting conditions. It is not clear if the same migration and/or entry pathways are utilized when secondary lymphoid tissues are activated during an immune response. Previous investigations in our lab have shown that T cell subtypes display differential migration patterns to peripheral lymph nodes during an antigen-induced immune response. Additional studies began defining the intracellular signaling cascades and adhesion molecules that may be responsible for the observed differential migration. In the studies presented here, inhibitors of proteins in signaling pathway(s) known to be involved in lymphocyte adhesion and migration were used to identify the intracellular signaling cascades responsible for the observed differential migration. Further, examination of cryosectioned lymphoid tissue by immunofluorescence microscopy sought to elucidate involvement of the inhibited pathways in cellular localization in vivo and the expression of peripheral lymph node addressin in the recruitment of T cells to peripheral lymph nodes. Several possible intracellular signaling pathways (PI3K and ZAP70) and L-selectin (CD62L) were eliminated as the cause of the differential T cell migration during immune responses.

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