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Investigating Immunological Responses of WC1+ Gamma Delta T Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2018 Investigating immunological responses of WC1+ gamma delta T cells in cattle an turally infected with mycobacterium avium subspecies paratuberculosis (MAP) Saleh Mohammed Albarrak Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Allergy and Immunology Commons, Immunology and Infectious Disease Commons, and the Medical Immunology Commons Recommended Citation Albarrak, Saleh Mohammed, "Investigating immunological responses of WC1+ gamma delta T cells in cattle an turally infected with mycobacterium avium subspecies paratuberculosis (MAP)" (2018). Graduate Theses and Dissertations. 16305. https://lib.dr.iastate.edu/etd/16305 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Investigating immunological responses of WC1+ gamma delta T cells in cattle naturally infected with mycobacterium avium subspecies paratuberculosis (MAP) by Saleh M. Albarrak A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Immunobiology Program of Study Committee: Jesse M. Hostetter, Co-Major Professor Ray W. Waters, Co-Major Professor Douglas E. Jones Judith R. Stabel Brett A. Sponseller The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2018 Copyright © Saleh M. Albarrak, 2018. All rights reserved. ii DEDICATION This dissertation is dedicated to my parents, my wife, my daughters and my relatives and friends. iii TABLE OF CONTENTS Page LIST OF FIGURES ...............................................................................................................v LIST OF TABLES ............................................................................................................... vii ACKNOWLEDGMENTS .................................................................................................. viii ABSTRACT .......................................................................................................................... ix CHAPTER 1. GENERAL INTRODUCTION ......................................................................1 Statement of the Problem ........................................................................................................1 Central Hypothesis & Specific Aims .....................................................................................2 Dissertation Organization ......................................................................................................2 Literature Review ...................................................................................................................3 References ............................................................................................................................19 CHAPTER 2. WC1+ γδ T CELLS FROM CATTLE NATURALLY INFECTED WITH MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS RESPOND DIFFERENTIALLY TO STIMULATION WITH PPD-J ....................................................30 Abstract ................................................................................................................................30 Introduction ..........................................................................................................................31 Materials and Methods .........................................................................................................33 Results ..................................................................................................................................37 Discussion ............................................................................................................................41 References ............................................................................................................................47 CHAPTER 3. DIFFERENTIAL CYTOKINE EXPRESSION BY WC1+ γδ T CELLS AND TOTAL MUCOSAL CELLS IN THE ILEUM OF CATTLE NATURALLY INFECTED WITH MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS ...........58 Abstract .................................................................................................................................58 Introduction ..........................................................................................................................59 Materials and Methods .........................................................................................................61 Results & Discussion ...........................................................................................................63 References ............................................................................................................................69 iv CHAPTER 4. WC1+ γδ T CELLS DEPLETION ALTERS CYTOKINE PRODUCTION BY PBMCs OBTAINED FROM CATTLE WITH THE SUBCLINICAL FORM OF MAP INFECTION ..................................................................76 Abstract .................................................................................................................................76 Introduction ..........................................................................................................................77 Materials and Methods .........................................................................................................79 Results & Discussion ...........................................................................................................82 References ............................................................................................................................87 CHAPTER 5. GENERAL CONCLUSIONS ........................................................................96 Summary ...............................................................................................................................96 Directions for Future Studies .............................................................................................100 References ..........................................................................................................................102 v LIST OF FIGURES Page CHAPTER 1. GENERAL INTRODUCTION Figure 1 Schematic representation of the WC1 molecule indicating antibody biding sites ................................................................................................. 28 Figure 2 WC1+ T cells links the innate and adaptive arms of the immune system ........................................................................................................ 29 CHAPTER 2. WC1+ γδ T CELLS FROM CATTLE NATURALLY INFECTED WITH MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS RESPOND DIFFERENTIALLY TO STIMULATION WITH PPD-J Figure 1 Percentages of γδ T cells within (non-stimulated) peripheral blood lymphocytes ............................................................................................... 53 Figure 2 WC1+ γδ T cell subsets frequencies in the intestinal mucosa of control, subclinical and clinically infected cattle .................................................... 54 Figure 3 γδ T cells proliferative responses to MAP complex Ag, PPD-J ................ 55 Figure 4 γδ T cells IFN-γ response to MAP complex Ag, PPD-J ............................ 56 Figure 5 γδ T cells IL-10 response to MAP complex Ag, PPD-J. ........................... 57 CHAPTER 3. DIFFERENTIAL CYTOKINE EXPRESSION BY WC1+ γδ T CELLS AND TOTAL MUCOSAL CELLS IN THE ILEUM OF CATTLE NATURALLY INFECTED WITH MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS Figure 1 Photomicrographs of serial sections of bovine ileum stained with either HE for histopathological evaluation or ZN for MAP detection ................. 73 Figure 2 Photomicrographs of bovine ileal tissue sections in which WC1, IL-10 and TGF-β mRNA messages are detected by in situ mRNA hybridization ..... 74 Figure 3 Differences in regulatory cytokine gene expression in ileal tissues from non-infected, subclinical and clinically infected cattle .............................. 75 Figure 4 Differences in proinflammatory cytokine gene expression in ileal tissues from non-infected, subclinical and clinically infected cattle ..................... 75 CHAPTER 4. WC1+ γδ T CELLS DEPLETION ALTERS CYTOKINE PRODUCTION BY PBMCs OBTAINED FROM CATTLE WITH THE SUBCLINICAL FORM OF MAP INFECTION Figure 1 IFN-γ, IL-12, IL-4 and IL-10 production by PBMCs cultures stimulated for 24h with PWM, PPD-J or medium only .............................................. 92 Figure 2 Detection of intracellular IFN-γ in CD4+ T cells. ..................................... 93 vi Figure 3 Detection of intracellular IFN-γ in PBMCs cultures depleted of total γδ T cells (∆ γδ T cells) or WC1+ γδ T cells (∆ WC1+ γδ T cells) before stimulation for 24h with PPD-J or medium only ....................................... 94 Figure 4 IFN-γ, IL-12, IL-4 and IL-10 production by PBMCs cultures depleted of total γδ T cells (∆ γδ T cells) or WC1+ γδ T cells (∆ WC1+
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