利用不同疫苗佐劑探討不同肺部樹突細胞對於建立抗流感病毒的T細胞免疫反應所扮演的角色

To study the effects of adjuvants on dendritic cells in establishing T cell immunity against influenza virus

徐佑松(Yu-Sung Hsu)

指導教授 ： 楊宏志

國立臺灣大學/醫學院/微生物學研究所/碩士(2020年)

https://doi.org/10.6342/NTU202003420

摘要

樹突細胞對於活化抗流感病毒的T細胞免疫反應相當的重要，但是目前對於樹突細胞是如何調節形成肺部記憶型T細胞仍不是非常的清楚。目前發現的肺部樹突細胞主要有三群：CD103+的樹突細胞、CD11b+的樹突細胞以及單核球衍伸的樹突細胞。根據先前許多研究發現這三種樹突細胞對於建立肺部記憶型T細胞皆非常重要，但是哪一群樹突細胞對於建立肺部駐留記憶型T細胞扮演最主要的角色抑或是不同時間不同樹突細胞所扮演的角色目前仍不是非常清楚。本篇研究中發現，CpG最主要傾向刺激CD11b+樹突細胞，此外我也發現以PLGA包裹CpG以及OVA-I相較於其他疫苗佐劑的組別可以產生最多數量的肺部常駐型記憶T細胞。另外，我也更深入探討了之前比較少討論的肺部常駐型記憶T細胞的前體發現肺部T細胞中Runx3的表達量會隨著時間的推移而發生改變且與肺部常駐型記憶T細胞的前體的數目有一定的關係。最後，我發現以PLGA包裹CpG以及OVA-I所產生的肺部常駐型記憶T細胞的前體的數目有比其他組別還要多的趨勢，因此很可能是因為CpG所誘導產生的肺部常駐型記憶T細胞的前體數目就較多導致其最後所建立的肺部常駐型記憶T細胞也就較多。

關鍵字

流感疫苗 ； T細胞免疫

並列摘要

Dendritic cells play vital roles in establishing the T cell immunity against influenza virus infection. However, it is still unclear about how pulmonary dendritic cells ( DCs ) modulate the establishment of lung resident-memory T cells ( TRM cells ). There are three main subsets of DCs in lung: CD103+ DCs, CD11b+ resident DCs and monocyte-derived DCs. Many previous studies used the depletion systems to prove that each lung dendritic cell subset is important in establishing TRM cells; nevertheless, which subset of DCs play a dominant role in the formulation of DCs is still unknown. In this study, we found that each individual adjuvant can stimulate different subsets of DCs, and among them CpG seems to primarily stimulate CD11b+ DCs. In addition, we found that use of PLGA nanoparticles encapsulating CpG and antigenic class I MHC-restricted peptide could induce much more TRM cells than the other adjuvants. Besides, we analyze the TRM precursors, and found that the expression level of Runx3 is related to the numbers of TRM precursors. Furthermore, nanoparticles encapsulating CpG and antigenic class I MHC-restricted peptide can induce more TRM precursors. In summary, CpG can induce more TRM precursors and this might be the reason that CpG can induce more TRM cells.

並列關鍵字

Influenza vaccine ； T cell immunity

參考文獻

1. Florian Krammer et al. 2018. Influenza. Nature Review Disease Primers. 4(1):3.

2. Mirco Schmolke et al. 2010. Evasion of innate and adaptive immune responses by influenza A virus. Microreview.12(7):873-80

3. Cécile Viboud et al. 2016. First flu is forever. Epidemiology. 354(6313):706-707

4. Saranya Sridhar et al. 2016. Heterosubtypic T-Cell immunity to influenza in Humans: Challenges for Universal T-Cell influenza vaccines. Frontiers in immunology. 7:195.

5. Jie Sun et al. 2013. Role of T cell immunity in recovery from influenza virus infection. Curr Opin Virol. 3(4):425-9