Regulation of Humoral Immunity to Allogeneic Platelet Transfusion Open Access

Gilson, Christopher (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/6108vb364?locale=en
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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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