Title Page
ABSTRACT
Contents
LIST OF ABBREVIATIONS 13
INTRODUCTION 15
MATERIALS AND METHODS 21
1. Mice 21
2. Antibodies and flow cytometric analysis 21
3. Intracellular cytokine assay 23
4. Administration of IL-4 and anti-IL-4 antibody in vivo 23
5. Influenza Virus Infection 24
6. Plaque assay 24
7. Reverse-transcription Quantitative PCR 25
8. ELISA 25
9. RNA extraction 26
10. Data processing 27
11. Aligning reads to reference genome 27
12. Statistical analysis of gene expression level 28
13. Data analysis 29
14. Apoptosis in vitro 29
15. statistical analysis 30
RESULTS 31
DISCUSSION 103
REFERENCES 110
국문 초록 122
Table 1. Upregulated DEGs in TM vs naïve CD8 T cells 58
Table 2. Interleukin-2 signaling pathway 65
Table 3. Upregulated DEGs in naive vs TM CD8 T cells 66
Table 4. Upregulated DEGs in Ly6C⁻ (Q3 and Q4) vs Ly6C⁺ (Q1 and Q2) VM CD8 T cells 72
Table 5. Upregulated DEGs in Ly6C⁺ (Q1 and Q2) vs Ly6C⁻ (Q3 and Q4) VM CD8 T cells 75
Table 6. IL-15-related genes compiled from literature 76
Table 7. Upregulated DEGs in Ly6C⁺ Sca-1⁻ (Q1) vs Ly6C⁺ Sca-1⁺ (Q2) VM CD8 T cell subsets 85
Table 8. Upregulated DEG in Ly6C⁺ Sca-1⁺ (Q2) vs Ly6C⁺ Sca-1⁻ (Q1) VM CD8 T cell subsets 86
Table 9. Upregulated DEGs in Sca-1⁺ (Q2 and Q3) vs Sca-1⁻ (Q1 and Q4) CD8 T cell subsets 100
Table 10. Upregulated DEGs in Sca-1⁻ (Q1 and Q4) vs Sca-1⁺ (Q2 and Q3) VM CD8 T cell subsets 102
Figure 1. IL-4 and anti-IL-4 antibody complex (IL-4C) treatment protected mice from lethal influenza A virus infection. 32
Figure 2. IL-4C treatment enhanced the accumulation of CD8 T cells, influenza-specific and bystander CD8 T cells. 35
Figure 3. Anti-CXCR3 antibody inhibited IL-4C-induced CD8 T cell accumulation in the lungs. 40
Figure 4. The number of innate immune cells in the lungs was similar between control and IL-4C-treated mice. 42
Figure 5. Antibody levels and virus titers in infected mice were not significantly different. 43
Figure 6. Development of Sca-1⁺ VM CD8 T cells is dependent on type I IFN signaling. 47
Figure 7. Development of Ly6C⁺ Sca-1⁻ VM cells was partially defective IL-4 mice. 49
Figure 8. Ly6C⁺ VM CD8 T cells are susceptible to IL-15 signaling. 51
Figure 9. RNA-Seq analysis results reveal the relationship between CD8 T cell subsets and the top 10 enriched pathways in TM and... 56
Figure 10. DEGs of top 10 upregulated pathways in TM vs naïve CD8 T cells were compared across the all subsets of CD8 T cells. 64
Figure 11. Pathway analysis highlighted the top 10 enriched pathways in Ly6C⁺ and Ly6C⁻ VM cells. 71
Figure 12. IL-15 plays an essential role in the development Ly6C⁺ VM CD8 cells. 79
Figure 13. Survival of Ly6C⁺ VM CD8 cells is IL-15 dependent. 82
Figure 14. Pathway analysis of RNA-Seq results presented the enriched pathway between IL-4-dependent (Ly6C⁺ Sca-1⁻) and type... 84
Figure 15. IL-4R, but not type 1 IFN receptor, is differentially expressed in VM CD8 T cell subsets. 90
Figure 16. Exogenous IL-4 treatment primary affects Ly6C⁻ VM CD8 T cells. 93
Figure 17. Complement pathway is dominant in Sca-1⁺ VM CD8 T cells. 98