Regulation of Humoral Immunity to Allogeneic Platelet Transfusion Público

Abstract

Abstract
Regulation of Humoral Immunity to Allogeneic Platelet Transfusion

By
Christopher R. Gilson
Platelet transfusion is an essential treatment for thrombocytopenia, which can result
from a wide range of conditions including acute hemorrhage, hematological malignancies,
hematopoietic stem cell transplantation, and congenital platelet disorders. A life-saving
therapy, transfusion may also carry significant risks. Anti-donor antibodies can be
developed and abrogate the efficacy of transfused platelets. Increasingly sophisticated
methodologies, including leukoreduction and irradiation of platelet products have decreased
the incidence of anti-donor antibodies by limiting the recipient's exposure to antigenic white
blood cells. In spite of these efforts, alloimmunization following platelet transfusion still
occurs in a significant percentage of patients.

Table of Contents

Table of Contents
Chapter 1 - Introduction

.............................................................................................. 1

Clinical significance of platelet alloimmunization ................................................... 2

A brief retrospective of transfusion medicine........................................................... 3

Development of platelet transfusion as a therapeutic modality ................................ 5

General platelet physiology ...................................................................................... 6

Clinical platelet storage and transfusion ................................................................... 9

Platelet refractoriness ............................................................................................... 11

Allospecific T cell activation ................................................................................... 12

Humoral response to platelet transfusion.................................................................. 14

Much ado about platelets ......................................................................................... 16
References ...................................................................................................................... 18

Chapter 2 - MHC Class II on Transfused Murine Blood is Not Required for
Alloimmunization Against MHC Class I .................................................................... 33
Abstract ........................................................................................................................... 34
Introduction..................................................................................................................... 35
Materials and methods .................................................................................................... 38
Results ........................................................................................................................... 40
Discussion ....................................................................................................................... 42
References....................................................................................................................... 45
Figure Legends................................................................................................................ 48

Chapter 3 - Characterization and Visualization of the Allogeneic Platelet
Specific CD4+ T cell Response ..................................................................................... 54
Abstract ........................................................................................................................... 55
Introduction..................................................................................................................... 56
Materials and methods .................................................................................................... 58
Results ........................................................................................................................... 62
Discussion ....................................................................................................................... 66
References....................................................................................................................... 71
Figure Legends................................................................................................................ 78

Chapter 4 - A Novel Mouse Model of Red Blood Cell Storage and Post-
Transfusion in Vivo Survival ...................................................................................... 87
Abstract ........................................................................................................................... 88
Introduction..................................................................................................................... 89
Materials and methods .................................................................................................... 91
Results ............................................................................................................................ 95
Discussion ....................................................................................................................... 98
References....................................................................................................................... 102
Figure Legends................................................................................................................ 105

Chapter 5 - Discussion ................................................................................................. 111
Summary ......................................................................................................................... 112

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Discussion ....................................................................................................................... 115

To leukoreduce or not to leukoreduce....................................................................... 115

Leukoreduction of platelet units ............................................................................... 116

Modeling platelet isolation and collection in a murine setting ................................. 119

Recipient T cell response to allogeneic platelet transfusion ..................................... 121

Modeling blood component storage in murine systems............................................ 123

Prevention of platelet alloimmunization ................................................................... 125
Future Directions............................................................................................................. 128

Short term future directions ...................................................................................... 128

Long term future directions....................................................................................... 131
General conclusions ........................................................................................................ 134
References....................................................................................................................... 135



List of Figures

Chapter 2

Figure 2.1 .................................................................................................................. 50

Figure 2.2 .................................................................................................................. 51

Figure 2.3 .................................................................................................................. 52

Figure 2.4 .................................................................................................................. 53

Chapter 3

Figure 3.1 .................................................................................................................. 82

Figure 3.2 .................................................................................................................. 83

Figure 3.3 .................................................................................................................. 84

Figure 3.4 .................................................................................................................. 85

Figure 3.5 .................................................................................................................. 86

Chapter 4

Figure 4.1 .................................................................................................................. 107

Figure 4.2 .................................................................................................................. 108

Figure 4.3 .................................................................................................................. 109

Figure 4.4 .................................................................................................................. 110


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About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Health Sciences, Immunology
Palabra Clave	platelet transfusion
Committee Chair / Thesis Advisor	Zimring, James C, Emory University
Committee Members	Selvaraj, Periasamy, Emory University Kirk, Allan D, Emory University Altman, John D, Emory University Mittler, Robert S, Emory University

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